News Archive

This archive captures news reported in previous months about the biosimilar industry. Visit Industry News to find the most recent developments.

July 2018   +

GLOBAL: Janssen critiques systematic review on biosimilar switching studies – and authors defend it

The journal Drugs has published a letter to its editor1 concerning a recent systematic literature review2 that showed a low risk of safety concerns or loss of efficacy after switching from an originator biologic to a biosimilar. The letter’s authors, all of whom report affiliations with Janssen Pharmaceuticals, say that switching is a beneficial topic for exploration, but criticized the review for “over-interpretation of the available data.” The authors have, in turn, defended their review with specific counter-arguments, outlined below.

Criticisms of systematic review Study authors’ response
A clear objective, outcome specification, and grading of the quality of evidence were lacking; the data should also have been weighted to reflect their relative strength.
Our intent was to neutrally assess whether there is any credible and consistent evidence that switching from originator biologics to biosimilar biologics is problematic. We stand by our conclusion that the overall finding remains clear and unambiguous, and is what would be expected when the authors of 88 out of 90 publications reach similar conclusions about their own individual study results.
The number of innovator biologics, diseases states, populations, study types, and study outcomes included are too diverse to apply a single approach to the review and draw any specific conclusions.
We consider that the diversity of products studied, and the diversity of indications, study designs, endpoints, and analyses of individual studies in our review is in fact a strength and not a weakness.
Randomized clinical trials and real-world evidence that showed unfavorable outcomes associated with switching from reference to biosimilar infliximab were available before the cut-off date but were not included in the review, and results from studies that show higher rates of discontinuation or adverse clinical outcomes in patients who switched to a biosimilar were not described.
We attempted to be as inclusive as possible with the literature and did not censor for positive or negative results. In cases of elevated discontinuation rates in individual studies, there are additional findings – sometimes from the same studies – that indicate no meaningful change in clinical outcomes. It is inappropriate to select specific data points while ignoring the totality of evidence from the same study.
The conclusion that there are no differences in efficacy or safety for every biologic and its corresponding biosimilars, based on the findings of switching studies with unrelated molecules, should be questioned; further study is needed.
It is inappropriate to impose an additional research burden on biosimilars that is not applied to other biologics, especially when there is no credible basis for this assertion. Our survey, with more than 14,000 patients in a total of 90 studies, provides stronger evidence than any individual study could be expected to provide.
The switching studies included are insufficient to demonstrate interchangeability according to the US Food and Drug Administration’s (FDA’s) draft guideline.
This comment is not relevant to our review because these studies were designed to assess the clinical impact of multiple switches and not to fulfill a specific regulatory requirement. A designation of interchangeability is a regulatory interpretation beyond the clinical evidence that we have reviewed.



  1. Pires A, Goyal K, Greenspan A. Comment on: Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. [Published online May 21, 2018.] Drugs. doi: 10.1007/s40265-018-0918-2.
  2. Cohen HP, Blauvelt A, Rifkin RM, et al. Author’s reply to Pires A, et al: Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. [Published online May 21, 2018.] Drugs. doi: 10.1007/s40265-018-0919-1.

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USA: FDA approves first biosimilars of epoetin alfa and pegfilgrastim – after rocky road

After a couple of misfires, Pfizer has finally won approval from the US Food and Drug Administration (FDA) for its biosimilar of anemia drug Epogen®/Procrit®. The FDA approved Pfizer’s Retacrit® (epoetin alfa-epbx) for the treatment of anemia caused by chronic kidney disease, chemotherapy or use of zidovudine in patients with HIV infection – and for use before and after surgery to reduce the chance of requiring a red blood cell transfusion. Retacrit® had been rejected by the FDA twice – the first time (in 2015) due to provision of insufficient data and the second time due to perceived problems at Pfizer’s manufacturing plant in Kansas, USA. Some commentators have criticized the delay in approving Retacrit® – a delay which has meant that, in the intervening time, a newer, still-patented version of the same protein, which requires less frequent dosing, has already superseded most uses of the original product. It has been pointed out that, to meet the FDA's requirements, Pfizer ended up testing Retacrit® in 2458 patients, while the trials for the originator, conducted from 1987 to 1989, had involved just 358 patients.

In another landmark biosimilar approval, the FDA has approved Mylan and Biocon’s pegfilgrastim biosimilar, Fulphila (pegfilgrastim-jmdb). The drug is approved to lower the incidence of infection caused by febrile neutropenia in patients receiving myelosuppressive chemotherapy, but, like the originator Neulasta®, is not approved for mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. The approval – which came just days after Health Canada approved Apotex’s biosimilar of pegfilgrastim (the first such approval in a highly regulated market) – is considered a breakthrough in an area where biosimilar manufacturers have faced a specific and protracted struggle with the fact that they were dealing with a pegylated molecule. Mylan itself – and other biosimilar manufacturers – had failed to secure either FDA or European Medicines Agency (EMA) approval for their pegfilgrastim biosimilar candidates, until now.

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USA: President Trump’s drug pricing plan includes measures to boost biosimilars

In President Donald Trump’s long-anticipated speech on reducing the price of drugs for American patients (“American Patients First”), promises were made to “derail the gravy train” that encourages higher drug prices, give Medicare Part D more ability to negotiate drug prices, end practices that “allow the middleman to pocket rebates and discounts that should be passed to patients,” and “get tough on drugmakers that exploit our patent laws.” Health & Human Services (HHS) Secretary, Alex Azar, also proposed greater public transparency on drug prices (e.g. within direct-to-consumer advertising) and a reconsideration of the role of pharmacy benefit managers (PBMs), who are currently allowed to receive undisclosed rebates from manufacturers in return for preferential coverage of their products. In addition, the new plan calls on the US Food and Drug Administration (FDA) to issue guidelines that would prevent originator biologic manufacturers from “abusing” Risk Evaluation and Mitigation Strategy (REMS) programs to stall the development of biosimilar competitors – and to improve the biosimilar approval process, including the long-awaited interchangeability designation. FDA Commissioner, Scott Gottlieb, added in a separate statement that the FDA will soon release its Biosimilar Action Plan to help facilitate the development and approval of biosimilars. Stakeholders from across the healthcare landscape responded positively to the plan, but some added that “we will not celebrate until more concrete action is taken.” Despite the administration’s suggestion that “middlemen” such as PBMs, will take a more limited role in the healthcare system under the blueprint, PBM Express Scripts said in a statement that it looks forward to working with the administration on “pro-patient, pro-payer policies.” Meanwhile, several commentators observed that the plan spares the pharmaceutical industry itself of the reforms they most vehemently oppose – underlined by the fact that drugmaker stocks jumped immediately following the President's speech. Others felt that – while the plan seems politically “tepid” – some elements are “eminently sensible” and show that the President has taken appropriate advice. HHS is inviting all stakeholders and interested parties to submit comments on the blueprint by July 16, 2018.

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USA: Commonwealth Fund survey finds Americans' concerns over healthcare costs growing

The Commonwealth Fund has released new findings from its Affordable Care Act Tracking Survey (a nationally representative telephone poll that tracks coverage rates among 19–64-year olds). The survey found that respondents (n=2403) continue to worry about healthcare costs on all fronts, from general medical bills to the high cost of prescription drugs. When asked if they would have the money to pay a $1000 medical bill within 30 days in the case of an unexpected medical emergency, 46% of respondents said no. Specifically, women, people of color, people who are uninsured, those with low incomes, and those covered by Medicare or Medicaid, were among the most likely to say they couldn’t pay the bill. When asked if they were confident in their ability to afford healthcare if they were to become seriously ill, only 62.4% of adults thought they would be able to manage, down from nearly 70% in 2015.

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USA: ADA issues white paper addressing the escalating cost of insulin

The American Diabetes Association (ADA) has released a set of policy recommendations highlighting the increasing difficulties patients with diabetes have with affording insulin or gaining access to this essential medication through their health insurance. The recommendations follow the findings of a working group that were presented to the Special Senate Committee on Aging earlier this month. The cost of diabetes in the United States was $327 billion in 2017, a 26% jump from 2012. That figure includes $31 billion for medication, including $15 billion for insulin. The public policy statement provides recommendations in four areas, the first of which is “streamlining the path to approval and accessibility of biosimilar insulins.”

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USA: New England Journal of Medicine publishes new review article on biosimilars in the US

Four senior US oncologists (including one representing ASCO) have co-authored an article published by the New England Journal of Medicine entitled “Rationale, Opportunities, and Reality of Biosimilar Medications.” The authors observe: “The potential for biosimilars to mitigate rising healthcare costs while improving access to highly effective therapies provides a true opportunity to reduce disparities in access to care and limit the financial burden of new treatments for cancer and other major illnesses.” However, they warn that “considerable professional and patient education will be important, along with rational and sustainable policies, to ensure the appropriate and effective use of biosimilar medications in clinical practice.”

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USA: New draft guidance issued on formal meetings between FDA and biosimilar sponsors

The US Food and Drug Administration (FDA) has released new draft guidance on formal meetings between itself and biosimilar sponsors – replacing previous guidance from November 2015. As previously, the guidance features sections on the five types of biosimilar biological product development (BPD) meetings – biosimilar initial advisory (BIA), Type 1, Type 2, Type 3, and Type 4. Type 1 meetings include discussions on clinical holds “in which the requester seeks input on how to address the hold issues; or (2) in which a response to hold issues has been submitted, and reviewed by the FDA, but the FDA and the requester agree that the development is stalled, and a new path forward should be discussed.” The draft also discusses what points should be included in meeting requests and the timelines for response. In the case of Type 2 meetings, scheduling timeframes have been extended from 75 to 90 days. The FDA notes there are three formats for meetings: face to face, teleconference/videoconference, and written response. Interested parties have been given until September 4, 2018 to comment on the draft guidance.

In the meantime, in a direct rule proposed in January 2018, the FDA has amended its inspection requirements of biological product establishments to promote greater efficiencies and less variability with originator biologic manufacturing, with the aim of easing the path for biosimilar makers. The direct rule is effective as of June 11, 2018 and applies to all licensed biologics.

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USA: AAPS releases white paper on best practice with analytical similarity evaluation of biosimilars

The American Association of Pharmaceutical Scientists (AAPS) has issued an open-access white paper entitled “Rational selection, criticality assessment, and tiering of quality attributes and test methods for analytical similarity evaluation of biosimilars.” Developed by an international, multidisciplinary team involving US Food and Drug Administration (FDA) and pharmaceutical industry experts, the white paper, published in the AAPS Journal, discusses scientific and methodological considerations on the three tiers of analytical similarity assessment recommend by the FDA, with specific examples to illustrate these principles. “Biosimilar developers face the difficult task of designing analytical studies capable of detecting relevant differences in structure and function from a licensed reference product, without access to detailed product knowledge. Generating compelling evidence of analytical similarity despite the paucity of available information requires a methodical approach to study design. In our paper, we lay out the emerging gold standard approach and illustrate the concepts discussed with examples from successful applications,” the authors note.

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USA: Dedicated research consortium focuses on real-world evidence generation for biosimilars

At the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) annual meeting in Baltimore, USA, members of the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) revealed the ways in which their organization (a not-for-profit entity that conducts post-marketing observational research) is working to provide real-world evidence on these products intended to heighten confidence in their safety and efficacy. The BBCIC uses the US Food and Drug Administration’s (FDA’s) Sentinel Initiative to monitor biosimilars using anonymized data from approximately 150 million patients. It is also able to make requests of its partners to provide specific data runs, via a secure network portal, that will be made available to stakeholders. The group is currently convening working groups that aim to improve the data it can provide, focusing on areas such as comparative effectiveness research methods and best practice in conducting switching studies.

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USA: New case study forecasts compelling financial benefits from adopting infliximab biosimilars alone

The Pacific Research Institute has publicized a new case study, based only on biosimilars of infliximab, to demonstrate how removing barriers to the use of biosimilars could benefit US patients, employers and taxpayers alike. The predictions indicated that:

  • Annual per-patient savings from use of an infliximab biosimilar instead of the originator, Remicade®, would range between $2100 and $4400.
  • If biosimilars grew to become one-half of the infliximab market, annual cost savings for employer-sponsored health plans would be as high as 8.4%, or between $262 million and $315 million.
  • Savings to taxpayers through lower Medicare costs from utilizing biosimilars could be as high as 8.1%, or $150 million in savings annually.
  • Collectively, there could be savings of $412 – $465 million a year, from maximizing the use of biosimilars for one drug alone.

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EUROPE: UK hospital reports a successful – and innovative – transition to biosimilar rituximab

At the annual meeting of the British Society for Haematology in April 2018, researchers from the University Hospital of Wales described its transition to the use of biosimilar rituximab in a real-world setting. To generate cost savings in the treatment of patients with B cell lymphomas, the hospital decided to transition from originator rituximab (Mabthera®) – which is given subcutaneously – to intravenous biosimilar rituximab. However, this change required an overhaul of the hospital’s chemotherapy service to accommodate the time and facilities needed to give the drug via infusion. The hospital took the opportunity to move chemotherapy treatments to offsite, nurse-led centers closer to many patients’ homes, including a mobile unit that could travel to meet patients’ needs. Nurses were given training to enable them to work without onsite medical support, and regular meetings with stakeholders were held to consider how best to streamline the process of delivering chemotherapy under the new system. According to the hospital’s representatives, feedback from patients was overwhelmingly positive, the overhaul of the hospital’s approach was achieved without an additional cost to the lymphoma service, and use of the biosimilar generated a substantial cost saving. The program is now set for expansion, which will free up capacity at the hospital for clinical trial activity.

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EUROPE: EC proposes manufacturing waiver for biosimilar exports

The European Commission (EC) has released a proposal aiming to boost investment and create more than 20,000 new jobs over 10 years by introducing a manufacturing waiver for the export of biosimilar and generic products outside of the European Union (EU). The proposal is meant to tackle problems caused by the EU’s supplementary protection certificate (SPC) system. SPCs were first introduced in 1992 to compensate originator manufacturers for the loss of patent protection time caused by a lengthy R&D process prior to licensing. However, SPCs have also prevented EU-based biosimilar manufacturers from exporting their products to countries where SPC protection is not in force. The new proposal would preserve SPC protection within the EU but would enable EU-based manufacturers of generics and biosimilars to compete outside of the EU on an equal footing with non-EU manufacturers.

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CANADA: Health Canada approves Apotex’s pegfilgrastim biosimilar

Just days before the US Food and Drug Administration (FDA) approved Mylan’s pegfilgrastim biosimilar, Apotex achieved approval from Health Canada for its own biosimilar version of Amgen’s originator Neulasta®. Apotex’s product – Lapelga – was therefore the first pegfilgrastim biosimilar to be approved in a highly regulated market. Apotex has submitted its product to The Canadian Agency for Drugs and Technologies in Health, the nation’s independent health technology assessment body, at a 25% discount to the list price of Neulasta®, generating a saving of Can $626.24 (approximately $484 USD) per 6-mg prefilled syringe. Currently, Neulasta®, at its average cost of approximately Can $12,525 (approximately $9687 USD) for a patient receiving 5 cycles of chemotherapy, is not reimbursed under drug plans in many Canadian provinces, or is restricted.

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June 2018   +

GLOBAL: AbbVie focuses on potential Humira® successor as biosimilar competition looms

AbbVie has announced positive top-line results from its Phase 3 SELECT-COMPARE clinical study that compared upadacitinib, an oral (non-biologic) Janus kinase (JAK) inhibitor, versus placebo, and versus Humira® (adalimumab) in patients with rheumatoid arthritis (RA).

  • In SELECT-COMPARE, upadacitinib (15 mg, once-daily) met both primary endpoints, with 71% of patients achieving ACR20* and 29% achieving clinical remission at Week 12.
  • All ranked secondary endpoints were also met, with significantly more patients on upadacitinib achieving low disease activity (45%) and ACR50* (45%) at Week 12 compared with those treated with adalimumab (29% for both endpoints).
  • Upadacitinib significantly inhibited radiographic progression at Week 26 compared with placebo.
  • The safety profile of upadacitinib was consistent with previously reported results, with no new safety signals detected.

The data from this study continue to support AbbVie’s goal of finding a new foothold in the RA space after it loses its patent exclusivity for Humira®, allowing adalimumab biosimilars to enter the market. According to a recent statement, AbbVie plans global regulatory submissions for upadacitinib for RA later this year.

*Symptomatic improvement based on American College of Rheumatology criteria (20% or 50%).

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GLOBAL: Analysis of global medical literature shows exponential increase in biosimilar research

The quality and quantity of worldwide research on biosimilars is increasing exponentially, according to the first published bibliometric analysis of biosimilars, by Hernández-Vásquez et al, in the Journal of Pharmaceutical Policy and Practice. Bibliometric analysis is used to objectively measure current research into a subject and its international scientific influence. The researchers found that the number of documents published on biosimilars had risen from three in 2004 to 521 in 2016 (P<0.001). Terminology associated with biosimilar publications was also observed to change over the years. Terms such as “legislation,” “structure,” “protein,” and “generic” dominated in the earlier range of years examined, whereas more recently, specific diseases and drugs were the top terms used, mirroring the overall trends associated with biosimilar development.

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GLOBAL: Global report highlights unequal access to biologics and biosimilars for IBD

The European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA), an umbrella organization that represents 34 patient associations around the world, has released a new report on healthcare inequities among nations and regions. In the report, the EFCCA identified disparities in access to biologics and biosimilars for the treatment of inflammatory bowel disease (IBD), identified from a survey of 32 national associations.* While the originator biologics adalimumab (Humira®) and infliximab (Remicade®) are approved to treat IBD diagnoses in all the participating countries, some countries have notable regional differences in availability and reimbursement, and some state a range of pre-conditions for treatment. Biosimilar infliximab (Inflectra®), is approved to treat IBD in 27 nations (84%) but, again, coverage is sometimes partial and 15 nations state various pre-conditions for treatment. Furthermore, the same molecule, when marketed as Remsima®, had additional differences in availability and coverage compared with the Inflectra® brand.

*Associations participating in the survey represented Argentina, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Malta, New Zealand, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, and the United Kingdom.

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USA: Biosimilar state legislation may thwart federal law

During a session at the Academy of Managed Care Pharmacy’s (AMCP) Annual Meeting, held April 23–26, 2018, in Boston, MA, USA, Reginia Benjamin, Director of Legislative Affairs for the AMCP, provided an in-depth look at state legislation on biosimilars. As well as summarizing the current status of such legislation, she highlighted how state laws may undermine and confound the intent of the US Food and Drug Administration (FDA). The history of state legislation was briefly summarized as follows:

  • 2013: The first legislation required pharmacists to notify prescribers by phone or fax within a specified time-period if they intended to dispense a biosimilar. There were also labeling requirements and additional record-keeping that were not required for other drugs dispensed.
  • 2014: New laws added provisions that notification could be achieved by adding a note into an electronic health record, so pharmacists would no longer have to phone or fax.
  • 2015: An entry into a pharmacy benefit manager’s system that was accessible to the prescriber was deemed as acceptable notification.
  • 2016: Notification and labeling requirements arose for dispensing an interchangeable biosimilar.
  • 2017/2018 (to date): No additional provisions.

Currently, 41 states and Puerto Rico, have laws addressing biosimilars and interchangeable biosimilars. The following requirements vary across states:

  • Notice to the patient required prior to dispensing a biosimilar.
  • Approval by the patient required prior to dispensing.
  • A timeframe for notice that varies from 24 hours up to 10 days.
  • Additional labeling requirements and record-retention timeframes.
  • Level of liability for a pharmacist who dispenses a biosimilar or interchangeable biosimilar (compared with that incurred by dispensing a different drug).

Significant issues and challenges with current state legislation were highlighted as follows:

  • State laws are not consistent with the Biologics Price Competition and Innovation Act’s (BPCIA) intent, which is to support price competition and innovation in the market, balanced with consumer interests.
  • Generally, there is no authority for pharmacists to substitute a biosimilar deemed interchangeable by the FDA for the reference product without the approval of the prescriber.
  • States do not use the FDA’s definition of interchangeable biosimilars. Instead, they refer to language in the original BPCIA. State laws have also given interchangeability a two-part definition: A biologic product determined by the FDA to meet the standards of interchangeability set forth in the BPCIA, or a biologic product determined by the FDA to be therapeutically equivalent as set forth by the FDA’s Orange Book – even though the Orange Book is for small-molecule drugs and not biologics.
  • Generally, there is no recognition of the FDA’s Purple Book, which lists licensed biologic products and whether they have approved biosimilars/interchangeable biosimilars.
  • States will probably continue to enact laws that are not consistent with the intent of the BPCIA and will likely change the BPCIA definitions and create barriers to dispensing.
  • Patient and prescriber confidence in these FDA-approved products may be hindered by restrictive state laws.

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USA: US biosimilar utilization management strategies are often clinically flawed, report finds

Healthcare consultancy Avalere has issued a new report concluding that many biosimilar utilization management strategies, including preferential formulary design and step therapy, are not only impeding the uptake of biosimilars in the US but are also clinically flawed. The report’s authors assessed commercial plan coverage and formulary design concerning biosimilars for the top 25 payers, covering approximately 189 million lives. Of the plans reviewed, 18 had available documents related to infliximab and its biosimilars:

  • Ten plans required use of the reference infliximab, Remicade®, first (alone, or in combination with a disease-modifying antirheumatic drug [DMARD]). Only one plan required the use of the biosimilar (Inflectra®) first, and only one plan allowed either Remicade® or Inflectra® to be used first-line.
  • Two plans required 12- or 14-week treatment periods to demonstrate treatment failure.
  • Four plans have different policies for the use of infliximab biosimilars in different approved indications.

The report highlights that, in many cases of step therapy that require a patient to start with an originator biologic, the biosimilar of the same product will only be covered if the patient fails to respond adequately to the originator. This demonstrates a fundamental lack of understanding that a biosimilar is highly unlikely to work if its originator does not and contradicts the European League Against Rheumatism’s (EULAR) recommendations that switching to another drug – not to a biosimilar of the same drug – is needed in the case of treatment failure. The authors write that, while it is to be expected that payers will act to protect their short- to medium-term financial interests, the extent to which such biosimilar utilization policies are necessary or clinically appropriate is questionable.

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USA: US patient group calls for Federal Trade Commission to investigate AbbVie’s biosimilar deals

The US patient advocacy group Patients for Affordable Drugs (P4AD) has called on the Federal Trade Commission (FTC) to examine whether a so-called “pay-for-delay” deal struck between AbbVie (makers of Humira®) and biosimilar developer Samsung Bioepis violates anti-competitive and antitrust laws. The deal is the second such agreement AbbVie has made; the first was with Amgen. In both cases, the agreement holds off the US market entry of adalimumab biosimilars until 2023, giving AbbVie five more years free of biosimilar competition. “AbbVie is using pay-for-delay deals to keep a cheaper product off the market and patients are the victims. We believe it is illegal and anti-competitive, and we are asking the FTC to step in and protect patients from AbbVie’s price hikes,” said David Mitchell, President and Co-founder of P4AD. The statement added: “Humira® is incredibly expensive. Over the past 5 years, the price has more than doubled. Its most recent price increase of 9.7% in January of this year (2018) will cost the US healthcare system $1.2 billion. We have patients all over the country who are hurt by these pay-for-delay deals.” P4AD has also encouraged patients to write to their Senators in support of changes that would put an end to such settlements, and says that, to date, more than 1200 patients have written to show their support.

In response, AbbVie has stated: “AbbVie’s settlements with Amgen and Samsung Bioepis are in no way pay-for-delay arrangements. AbbVie is not paying Amgen or Samsung Bioepis, and in fact both Amgen and Samsung Bioepis will be paying royalties to AbbVie once their adalimumab biosimilar products launch in the [United States].”

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USA: Research highlights evolving approaches to biosimilars in the US

At the Academy of Managed Care Pharmacy’s (AMCP) Annual Meeting, held April 23–26, 2018, in Boston, MA, USA , a number of research teams presented posters relevant to the US adoption of biosimilars.

  • A survey sent to health plan executives and pharmacy benefit managers (with 77 respondents) found that specialty pharmacy products continue to transition from fixed co-pays to percent co-pays, and more plans now cover physician-administered products under the medical benefit (44.1%, up from 15.2% in 2016). Only 53.1% of respondents expect biosimilars to be used across all of the reference product’s indications (down from 59.5% in 2016), and 44.9% expect to restrict approved indications (up from 31% in 2016). One quarter of plans expect that a biosimilar will be the only product available for some indications. Among the respondents, 45.1% expected less than a 10% savings from biosimilars in 2018, 47.1% expected a 10–20% saving by 2020, and 58% expected greater than a 20% saving by 2025.
  • Researchers from Magellan Rx Management and Magellan Health sought to analyze the impact of a “least cost alternative” cost-of-care program for ophthalmic injections administered under the medical benefit for the commercial and Medicare Advantage members of a regional health plan. A new fee schedule was implemented for three reimbursed intravitreal anti-VEGF drugs: aflibercept (Eylea®), ranibizumab (Lucentis®), and bevacizumab (Avastin® – an off-label use but commonly utilized in practice due to the significantly lower price). Reimbursement for bevacizumab was increased from market rate to a margin comparable to the other two products. After a year, annualized savings were $2.9 million for commercial plans, and $885 thousand for Medicare Advantage plans. The researchers say that such programs will become especially important when cost-saving biosimilars for these products reach the US market.
  • Researchers from the Sharp Rees-Stealy Medical Group in San Diego, California, USA, described their experience of working closely with physicians on biosimilar adoption. Since physicians commonly report that they have concerns about comparative response to biosimilars, safety, patient preference, and the limited data on antibody cross-reactivity between a reference and a biosimilar product, the authors found that “it is tough to pursue an aggressive strategy such as enforcing substitutions to biosimilars.” Instead of mandatory switching, the group is adopting a collaborative program requiring physicians to prescribe a biosimilar in treatment-naïve patients, and to consider a biosimilar during renewal of every prior authorization for a given therapy, though these protocols will not apply to patients with uncontrolled disease or known immunogenicity. Physicians will retain the right to disallow biosimilar substitution and safety and efficacy data will be collected on an ongoing basis.

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USA: Oncologist sees biosimilars playing a key role in the Oncology Care Model

An oncologist at a South Carolina practice has described the role that biosimilars can play in achieving the objectives of the Oncology Care Model (OCM). The OCM, a reimbursement model developed by the Centers for Medicare and Medicaid Services’ (CMS), Center for Medicare and Medicaid Innovation, allows oncology practices to enter into payment arrangements that include financial and performance accountability for episodes of cancer care. The model is intended to improve health outcomes and produce higher quality care at the same cost or a lower cost to Medicare. Kashyap Patel, MD, CEO of Carolina Blood and Cancer Care, reported that, as his practice has begun to implement OCM, it has moved 100% of its patients to biosimilar filgrastim (Zarxio®) from the reference filgrastim, Neupogen®. With an approximate 15% difference in cost between the two products, the change has saved the practice – and Medicare – valuable resources, and Patel sees the potential for savings to be even greater once biosimilar anticancer therapies reach the US marketplace. With the cost savings that his practice has achieved so far under OCM, Patel says that his clinic has been able to institute drop-in hours for patients who have any health concerns, even concerns that aren’t related to their cancer treatment. “The patients love it,” he said, and the practice has been able to refer patients to other specialists to address comorbidities that are impacting their overall health.

To date, Patel says that his patients have not had concerns about using biosimilar filgrastim instead of the originator. He explains that, in his rural South Carolina practice, many patients “are still using flip phones” and aren’t particularly concerned about the nuances of biosimilarity or the technicalities of the biosimilar approval pathway. Instead, they care about whether a treatment has been approved by the US Food and Drug Administration (FDA) and whether it is effective in treating their condition. “If I were practicing in Manhattan or in Beverly Hills,” he said, “these conversations might be different,” but even when anticancer biosimilars like trastuzumab and bevacizumab reach the clinic, Patel expects that mutual patient–provider respect will be the most important factor in patients’ acceptance of biosimilar drugs. Provider education, as well as patient awareness, remains a massive unmet need in bringing biosimilars into the clinic. In Patel’s view, it’s not just the oncologist who has to become more knowledgeable about biosimilars: nurses are a cornerstone of patient care. “Patients spend 6 hours with the infusion nurse while they may spend 15 minutes with me,” he said, adding that it’s human nature for some patients to be reticent about asking their physician questions about their treatment and may prefer to ask a nurse. As the anticancer biosimilars begin to make their way into the clinic, Patel plans to work on enhanced nurse education to help support and reassure patients as they undergo treatment.

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EUROPE: European regulators are open to novel strategies in biosimilar development, review finds

While the European pathway for biosimilar approval is older and more developed than that of the United States, regulation of biosimilars is still evolving. A new review published in the British Journal of Clinical Pharmacology explains that novel strategies are emerging in the development of biosimilars for the European market, and that regulators seem willing to consider these alternative strategies when scientifically justifiable. Approval of biosimilars appears possible even in cases where European Medicine Agency (EMA) guidelines have not been strictly followed. The authors examined European Public Assessment Reports (EPARs), as well as information from PubMed and clinical trials databases, on 17 EMA-approved biosimilars and made the following observations:

  • Submission of fewer data than officially required
    In the case of an approved enoxaparin sodium biosimilar, the product sponsor did not conduct Phase 3 studies (which were specified in product-specific guidance), only 20 healthy volunteers were included in a pharmacodynamic study, and no intravenous route of administration was included in a study. “In the case where a sponsor has a strong scientific rationale for a specific development [program], regulators in Europe still seem to be open minded to alternative development strategies, even for cases where a product‐specific guideline has already been issued,” write the authors.
  • Variable choice of study population
    Two biosimilars of etanercept have been approved in Europe, one on the basis of studies in patients with rheumatoid arthritis (RA), and one on the basis of studies conducted in patients with plaque psoriasis. The product-specific guidance on monoclonal antibodies indicates that the “most sensitive” patient population and clinical endpoint should be used in development, and the Committee for Medicinal Products for Human Use (CHMP) has indicated a preference for the RA population for etanercept. It is unclear why plaque psoriasis was selected by one of the two sponsors, but the product achieved approval nonetheless.
  • Non-inferiority studies used in place of equivalence studies
    Generally, biosimilar product sponsors are asked to show equivalence, not non-inferiority, of their products versus the reference drugs. However, in the cases of the two approved insulin glargine biosimilars and an approved rituximab biosimilar, the sponsors submitted data from non-inferiority studies.
  • Post hoc choice of equivalence margins
    In the case of an approved rituximab biosimilar, efficacy using the mean change from baseline in the 28‐joint Disease Activity Score was evaluated, and an equivalence margin was chosen after the fact and justified by historical data. The product sponsor also provided a second study with the same primary endpoint, using the same equivalence margin. It is not clear why the first study was presented as the pivotal efficacy study, though the choice of margins can be discussed and agreed upon with the EMA.
  • Increasing use of bridging studies, adaptive designs, and multiple switches
    While crossover designs remain the most frequently used study designs, six of the applications that the authors examined, used bridging studies – comparing the biosimilar with both a US-approved and EU-approved originator product – which may point to global development programs for the proposed biosimilars. Typically, these studies include 3-period crossover designs. Adaptive designs, in which there is no fixed sample size at the beginning of the trial, are also on the rise, with such designs reported in EPARs for approved biosimilars of teriparatide, insulin glargine, and adalimumab. Switching studies – such as one conducted for an approved etanercept biosimilar – are growing in popularity as well, likely because such studies are forward-looking approaches to addressing US regulatory requirements for demonstrating interchangeability.

The authors conclude that there is high variability among submitted applications for biosimilars, and that the EMA is open to considering approaches that deviate from official guidelines, provided there is appropriate scientific justification for this and sufficiently convincing totality of data to support a demonstration of biosimilarity.

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EUROPE: Sandoz takes unorthodox route to boosting biosimilars in the UK

Sandoz, the generics arm of Swiss drugmaker Novartis, has been closely collaborating with Jatinder Harchowal, Chief Pharmacist at London’s Royal Marsden Hospital, the UK’s leading cancer center, to shift roughly 80% of eligible patients from originator rituximab to a biosimilar version in only 6 months, achieving an estimated £80 million in savings for the UK’s National Health Service (NHS). Yet rather than continuing to use Sandoz’s biosimilar, the Royal Marsden has now chosen one manufactured by Napp Pharmaceuticals. Sandoz’s decision to invest in the project with no guarantee of an immediate commercial return highlights the potential it sees in a market, which it says will be worth $14 billion by 2020. Tim de Gavre, the company’s UK head, said: “We have a vested interest in creating a sustainable environment around biosimilars.” Building confidence among doctors and patients through such initiatives is seen as crucial to the uptake of biosimilars, especially in oncology. Emphasizing that the work could not have happened without the resources Sandoz was able to commit, Mr Harchowal said: “We felt that to engage the clinical mind and heart, you had to really make sure people understood how biosimilars were offering exactly the same clinical outcomes, with the same safety profile, but at a much cheaper cost.” The shift in the NHS’s stance is already evident. In the last financial year, it has saved £170 million by using three biosimilars – well on the way to a goal set by Simon Stevens, head of the health service in England, to save £300 million from this approach by 2021.

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EUROPE: European Biosimilar Medicines Conference highlights continued success with biosimilar adoption

Biosimilar experts from across the European Union (EU) have showcased how rapidly biosimilars have gained market share, in contrast to US and Canadian markets. Keith Ridge, Chief Pharmaceutical Officer at National Health Service (NHS) England, told attendees at the 16th Annual Biosimilar Medicines Conference in London, that the UK has seen increasing uptake of rituximab, infliximab, and etanercept biosimilars, particularly in London. For instance, a biosimilar for infliximab, which came to market in March 2015 is now used by about 80% of patients receiving infliximab in the UK. Per Troein, Vice President at IQVIA, also noted how Denmark and Norway are good examples of countries that have increased their uptake of infliximab biosimilars quickly because of their use of a tender system to pay for the medicines. Justin Stebbing, Professor of Oncology at Imperial College London, questioned if biosimilar developers will still have to run the large clinical studies currently needed to prove biosimilarity, given that the sensitivity of analytical comparisons is increasing. But the lingering question for Stebbing, which he said he grapples with daily, is how to explain to cancer patients what switching them to a biosimilar version of a medicine means, or if he should even try to explain the switch since the medicines are so similar.

Gustaf Befrits, a Health Economist with the Stockholm County Council in Sweden, noted that all the patients taking infliximab in Stockholm were switched to a lower-cost biosimilar in just 2 months, and very few expressed a negative opinion of the switch, though all patients were informed of the decision. As for as predictions for the next 10 years, Troein said he expects discounts in the EU of between 25% and 70% off the original list price will be common and result in “significant volume increases.” The issues of safety, switching, and extrapolation – all of which were question marks when biosimilars first came to market in the EU 12 years ago – “will largely be gone.”

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EUROPE: UK researchers report a successful switching program to biosimilar etanercept

Researchers at the British Society for Rheumatology’s Annual Conference in Liverpool, UK, have presented the outcomes of a multi-disciplinary switch to biosimilar etanercept (Benepali®) from the reference product Enbrel® in patients with rheumatoid arthritis (RA) (n=151) conducted between January and June 2017. Study participants were offered an education session as well as a dedicated biosimilar switching clinic staffed by a rheumatology consultant, a registrar, and specialty pharmacist both before the switch and 4 months afterwards. The switch was predicted to result in a cost saving of approximately $675,902 (£500,000) per year. It was found that, in a relatively short period of time, a large number of patients were able to safely switch to the biosimilar in a controlled setting without loss of efficacy or increased toxicity. In total, 8 patients were switched back to the reference product (5 of whom reported subjective adverse events and 3 of whom had difficulty using the auto-injector pen). Two patients experienced disease flares. When asked how they felt about their disease control after the switch, 75% of patients said they felt no different. In addition, the method of delivery of the biosimilar was preferred by most patients, who commented on the easier technique and reduced manual dexterity required to administer the drug.

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May 2018   +

GLOBAL: New IQVIA report predicts the “next large wave of biosimilars”

The IQVIA Institute for Human Data Science has released a new report on the global healthcare landscape in 2018 and beyond, in which the key role that biosimilars will play is highlighted. IQVIA predicts that, in one or more developed markets, $19 billion of current spending on biologics will become exposed to competition from biosimilars in 2018. Compared to just $3 billion that became exposed in 2017 (and added to the $26 billion already facing competition), the 2018 figures are striking. “The new exposure to competition in 2018 is the largest single-year change to date and signals the start of the next large wave of biosimilars” the report states. It also predicts that:

  • In the period 2019–2022, an additional $52 billion is expected to face biosimilar competition for the first time in developed countries, with the US market accounting for $37 billion of that sum.
  • By 2027, 77% of current spending on biologics will be subject to biosimilar competition.
  • Between 2018 and 2022, competition from biosimilars could bring down the total spend on biologics by 10% (i.e. by $50 billion).

However, spending on biosimilars versus originators will depend on factors such as the number of competitors, the speed with which competition enters the market, and the extent to which biosimilars compete on price. The timing of biosimilar competition itself depends on a variety of factors, including patent litigation. According to IQVIA, the top biologics that will face new or expanded competition in the territories of Japan, the Republic of Korea, Canada, the EU, and the US are: adalimumab (Humira®), insulin glargine (Lantus®), etanercept (Enbrel®), infliximab (Remicade®), rituximab (Rituxan®, MabThera®), bevacizumab (Avastin®), insulin aspart (Novolog®), insulin lispro (Humalog®), pegfilgrastim (Neulasta®), and trastuzumab (Herceptin®).

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GLOBAL: Second legal settlement by AbbVie relating to a prospective adalimumab biosimilar

Samsung Bioepis and Biogen have announced a settlement with AbbVie, makers of Humira®, which will allow them to launch their European Medicine Agency (EMA)-approved adalimumab biosimilar – Imraldi® – in the EU on October 16, 2018. The agreement allows the parties to dismiss all pending patent litigation and AbbVie will grant patent licenses for the sale and use of Imraldi® in Europe on a country-by-country basis. Imraldi® is not yet approved in the US, but AbbVie has stated that it will begin a license period for the biosimilar in the US market on June 30, 2023. The newly announced settlement is similar to the one that rival biosimilar developer Amgen struck with AbbVie in September 2017; under that deal, AbbVie will permit Amgen to launch its adalimumab biosimilar (Amgevita) in the EU on the same date as Imraldi®. Amgen’s product is also approved by the US Food and Drug Administration (FDA) (with the trade name Amjevita), but under the agreement with AbbVie, it cannot launch in the US before January 31, 2023 – i.e. 5 months before Imraldi®. This 150-day marketing advantage for the first FDA-approved adalimumab biosimilar suggests a benchmark for future patent litigation settlements – although Amgen’s biosimilar will not get a similar head start in Europe. A third adalimumab biosimilar, Boehringer Ingelheim’s Cyltezo®, is approved in the US but so far, a settlement between Boehringer Ingelheim and AbbVie has not been announced. Meanwhile, the price of Humira® continues to rise for US patients; AbbVie raised it by 9.7% for 2018 in a move that analysts say could add $1.2 billion to the US healthcare system’s costs for the year. The legal settlements AbbVie has negotiated have enabled commercial exclusivity of Humira® to continue for 20 years beyond its US launch.

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GLOBAL: RA study shows switching from Humira® to biosimilar adalimumab (Cyltezo®) has no clinical impact

Newly released 58-week data from the VOLTAIRE-RA trial (in Annals of the Rheumatic Diseases) demonstrates that switching from Humira® to Boehringer Ingelheim’s adalimumab biosimilar Cyltezo® had no impact on efficacy, safety, or immunogenicity. VOLTAIRE-RA (n=645) was a randomized, double-blind, parallel-arm equivalence trial conducted in 14 countries. Patients with moderate-to-severe rheumatoid arthritis (RA) who were stable on methotrexate (and had not been previously exposed to adalimumab or to more than one other biologic) were randomized to receive a 40 mg subcutaneous dose of either Humira® or Cyltezo® once every 2 weeks for 24 weeks. Patients in the Humira® group were re-randomized at week 24 to either continue with Humira® or switch to the biosimilar. At week 48, there was an option to enter an open-label extension in which all participants received the biosimilar. The researchers reported that the difference between the two arms in terms of the study’s co-primary endpoints - percentage of patients meeting the American College of Rheumatology’s criteria for a 20% improvement (ACR20) at week 12 (requested by the US Food and Drug Administration [FDA]) and week 24 (requested by the European Medicines Agency [EMA]) - were within the pre-specified margin required to demonstrate equivalence. There was also no significant difference between the groups in terms of adverse events or immunogenicity. The authors concluded that, together with analytical and Phase 1 data, the VOLTAIRE-RA findings suggest that the two products are therapeutically equivalent.

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USA: Americans fear medical costs more than serious illness, new survey finds

New survey findings released by NORC* at the University of Chicago (a non-partisan social research institution), together with the West Health Institute, has found that “healthcare costs have a significant and enduring impact on financial health.” Conducted in February 2018 among 1302 adults (providing a sample coverage of approximately 97% of US households), the survey found that:

  • 36% of respondents said that they had depleted their savings because of healthcare costs
  • 32% had taken on credit card debt or had borrowed money to pay for care
  • 30% felt that they had to decide between medical care and basic necessities
  • 41% said they could not add money to their savings because of medical bills
  • 25% had a medical bill referred to a collection agency.

Some respondents reported going without care because of the costs, skipping a medical test or treatment to save money (40%), and not filling a prescription (or taking less medication than prescribed) because of cost (32%). Among those who had skipped a test or treatment, 60% said that they were afraid of the cost of a serious illness, while only 47% said that they were afraid of the illness itself. According to the report, these fears about the cost of treatment are often based on prior experience. “It’s shocking and unacceptable that medical bills strike more fear in the hearts of Americans than serious illness,” Shelley Lyford, President and CEO of West Health Institute, said. “Americans are paying more for healthcare than they should and getting less than they deserve.”

*Originally established as the National Opinion Research Center.

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USA: Federal panel calls for urgent action to “align cancer drug prices with value”

A new report released by the President's Cancer Panel – a federal body which advises the US President on high-priority issues in cancer – has called for urgent action “to align cancer drug prices with value.” The panel's report, Promoting Value, Affordability, and Innovation in Cancer Drug Treatment, states that, while some cancer drugs have been transformative and may warrant prices that reflect their benefits, many new drugs do not provide benefits commensurate with their price tags. “Cancer patients should not have to choose between paying for their medications or paying their mortgages,” said Barbara K. Rimer, Chair of the panel. “This is a national imperative that will not be solved by any one sector working alone.” The panel highlighted that, when patients’ finances are strained, they are less likely to follow treatment regimens, potentially worsening the health outcomes that their drugs are intended to improve. The term “financial toxicity” was used to describe the negative impact of cancer care costs on patients’ well-being. Following a series of multi-disciplinary working groups, the panel identified six priorities that need immediate attention:

  1. Promote value-based pricing and use of cancer drugs.
  2. Enable meaningful communication about treatment options, including cost information, to support patients' decision-making.
  3. Minimize the contributions of drug costs to financial toxicity for cancer patients and their families.
  4. Stimulate and maintain competition in the generic and biosimilar cancer drug markets.
  5. Ensure that the US Food and Drug Administration (FDA) has appropriate resources to assess cancer drug safety and efficacy efficiently.
  6. Invest in biomedical research to create a strong foundation for developing innovative, high-value cancer drugs.

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USA: New report argues for shake-up of US policy if biosimilars are to succeed

A new report from US healthcare consultancy Avalere Health argues that, if a multi-source market for biologic drugs is to emerge in the US, originator biologics and biosimilars must be able to gain market share commensurate to the value they offer, and an environment that promotes true competition must be established. The report highlights the success of biosimilars in Europe – which has been driven by a variety of country-level policies – and compares the performance of biosimilars in markets that have set up specific incentives (e.g. Scandinavian countries and the UK), with those where no proactive policies are in force (e.g. Ireland and the Republic of Korea). In the US, with its young biosimilars market, payers contemplating covering a biosimilar product expect a discount of up to 40% to help offset the administrative costs of switching patients, implementing educational programs, and creating utilization management strategies. If the price of a biosimilar is too near that of the originator, there is little incentive to undertake such a process – and established contracts with originator product sponsors may further undermine competition. The report concludes that, “without specific incentives to help biosimilars achieve market share in exchange for competitive prices, a stable multi-source specialty market in the US may not flourish.”

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USA: “Not So Different” – a podcast from The Center for Biosimilars

The US-based Center for Biosimilars – an organization that “couples clinical and regulatory information with the economics of biosimilars to improve understanding and critical thinking in the field” – has released a podcast entitled: “Not So Different.” The podcast features expert viewpoints on biosimilars from physicians, pharmacists, patients, developers, and other stakeholders, discussing a range of key topics:

  • Episode 1: Interchangeability
  • Episode 2: Non-medical switching
  • Episode 3: Pricing
  • Episode 4: Creating a vibrant biosimilars market
  • Episode 5: Policy and biosimilars
  • Episode 6: State level legislation (covers state-level legislation concerning the substitution of interchangeable biosimilars, and how one specific piece of biosimilars-focused legislation led to the formation of the Nebraska Rheumatology Society).

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USA: CMS lowers maximum co-payment amount for biosimilars

The Centers for Medicare and Medicaid Services (CMS) has released its final rule for the Medicare program for the contract year 2019, which includes a key change to its approach to biosimilars. In the rule, CMS has said that it would lower the maximum co-payment amount for low-income subsidy (LIS) beneficiaries for biosimilars to match the lower co-pay amount required for generic and preferred multiple-source drugs. According to CMS, this new policy will reduce spending by approximately $10 million, and will help to reduce confusion in the marketplace surrounding this issue. However, CMS noted that it “does not have the flexibility” to establish a lower co-pay amount for biosimilars for non-LIS enrollees who are in the catastrophic phase of the Medicare Part D benefit. Meanwhile, nine US medical associations* have sent a joint letter to Health & Human Services Secretary Alex Azar in which they voice concerns about the President’s 2019 budget and the Council of Economic Advisers’ drug plan. The groups say that the proposal to enable Medicare Part D formularies to limit coverage of treatments could reduce patient access to high-cost biologic therapies (including biosimilars) that are judged by their physician to be the most appropriate choice for them.

*The American Academy of Dermatology Association, American Academy of Neurology, American Academy of Ophthalmology, American Academy of Physical Medicine and Rehabilitation, American College of Gastroenterology, American College of Rheumatology, American Gastroenterological Association, American Urological Association, and the Infectious Diseases Society of America.

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USA: FDA announces 5-year Biosimilar User Fee Act plan

The US Food and Drug Administration (FDA) has released its 5-year financial plans for its User Fee Acts, including the Biosimilar User Fee Act (BsUFA), which authorizes the agency to collect fees from biosimilar applicants for the review of candidate products. During 2018, FDA estimates that it will collect approximately $40 million in user fees and will carry over more than $48 million from the prior year. As FDA ramps up to meet this demand, it plans to hire 15 new staff members for its Center for Drug Evaluation and Research.

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EUROPE: UK’s National Health Service prepares for the arrival of biosimilar adalimumab

The UK’s National Health Service (NHS) has begun comprehensive preparations for the arrival of biosimilar adalimumab later this year. In a briefing to regional committees, commissioners were encouraged to plan for maximum utilization of the “best value” adalimumab option beginning in October 2018, when Amgen’s European Medicines Agency (EMA)-approved biosimilar, Amgevita, becomes available. According to the briefing, originator adalimumab (Humira®) cost the NHS over £333 million (approximately $469 million) to treat approximately 57,000 patients with home-administered subcutaneous injections from 2016 to 2017. The NHS hopes that using the “best value” adalimumab product will help it to achieve its 2021 goal of saving £200–£300 million (approximately $282–$422 million) annually. Using other approved biosimilars has already saved the NHS £170 million (approximately $239 million); currently 80% of infliximab-treated patients and 58% of etanercept-treated patients are receiving a biosimilar in the UK. An NHS working group to oversee use of the best-value adalimumab has been established using a commissioning framework (launched in September 2017), which proposes that at least 90% of treatment-naïve patients and 80% of patients currently receiving treatment should be prescribed the best-value biologic within 12 months of the launch of a biosimilar. Regional Medicines Optimization Committees are currently ensuring that appropriate commissioning plans are in place across England, working to remove barriers to biosimilar uptake, looking at additional tools to support and track the transition to biosimilars, and collaborating with patient advocacy groups on patient and public educational initiatives.

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April 2018   +

GLOBAL: New systematic review confirms biosimilars perform comparably to originators after switching

A major new systematic literature review published in the journal Drugs has reported that, in 90 biosimilar switching studies conducted in more than 14,000 individuals and involving 7 molecular entities used to treat 17 disease indications, switching to a biosimilar was not associated with emergent safety concerns or loss of efficacy. The impetus for the study was that, despite the lack of problems reported during more than 10 years and 700 million patient days of experience with biosimilars, some stakeholders remain cautious about switching to biosimilars in patients who are already stabilized on an originator drug. The authors report that the great majority of the publications assessed (including three large multiple switch studies) did not report any differences in immunogenicity, safety, or efficacy following a switch. The nature and intensity of safety signals reported after switching to biosimilars were the same as those already known from continued use of originators. Only two studies reported a loss of efficacy or increased dropout rates after a switch, but these findings were not replicated in a much higher number of other studies assessing the same switch (originator to biosimilar infliximab). The authors conclude that the two studies with adverse outcomes appear to be outliers. One of the authors, Gillian Woollett of Avalere Health, commented that the study “confirms the expectation already established though the application of sound regulatory science” and should help all stakeholders feel more comfortable with transitioning to biosimilars, even for patients who are already established on an originator biologic.

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GLOBAL: New data confirms noninferiority of biosimilar infliximab in IBD

At the 13th annual congress of the European Crohn’s and Colitis Organisation (ECCO) in Vienna, Austria, data from the 26-week open label extension phase of the NOR-SWITCH trial – focusing on the inflammatory bowel disease (IBD) subgroup – were presented. The extension study (n=380) compared uninterrupted treatment with biosimilar infliximab (CT-P13) through week 78 with switching from the originator product Remicade® to the biosimilar at week 52. The primary endpoint of the extension study was overall disease worsening during follow-up. The authors reported no difference between patients who remained on CT-P13 versus those who switched from Remicade®. They also confirmed that exploratory subgroup analyses of patients with Crohn’s Disease (CD) and ulcerative colitis (UC) showed similarity between the groups in terms of efficacy, safety, and immunogenicity. The data may provide reassurance to clinicians who had expressed concern that the main NOR-SWITCH trial (a 52-week double-blind study that demonstrated the noninferiority of switching from Remicade® to CT-P13 compared to continued treatment with Remicade®) was not powered to demonstrate noninferiority of the biosimilar in individual disease states, which included CD, UC, rheumatoid arthritis, psoriatic arthritis, and plaque psoriasis. ECCO delegates also heard 12-month data from the Personalized Anti-TNF therapy in Crohn’s disease Study (PANTS). Conducted in the UK, PANTS is a 3-year prospective study assessing 1,601 patients with active CD who had received no prior anti-TNF treatment. Participants were randomized to receive either originator infliximab (Remicade®), biosimilar infliximab, or originator adalimumab (Humira®). At the end of the 12-month study period, the remission rates were 40%, 40%, and 34% for the Remicade®, biosimilar infliximab and Humira® groups, respectively – confirming that, at one year, the biosimilar had performed comparably to its own originator biologic and to a major competitor.

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USA: FDA Commissioner Scott Gottlieb denounces “rigged” system that's impeding biosimilar uptake

As biosimilars languish in the US market and much of their potential savings go unrealized, a top government health official has brought the issue firmly into the spotlight. At the National Health Policy Conference for America's Health Insurance Plans (AHIP), Food and Drug Administration (FDA) Commissioner Scott Gottlieb took aim at what he called a “rigged” contracting system that's harming biosimilar adoption. Pharmacy benefit managers (PBMs), health insurers, and drug-makers were all criticized by Gottlieb for their part in the establishment of pricing constructs that profit the industry at the expense of consumers. The crux of the problem, Gottlieb explained, is the “rebate trap” which permits PBMs and insurers to profit from the spread between Wholesale Acquisition Cost (WAC) and the actual rebated price for an innovator therapy. “Patients shouldn’t face exorbitant out-of-pocket costs and pay money where the primary purpose is to help subsidize rebates paid to a long list of supply chain intermediaries. Sick people aren’t supposed to be subsidizing the healthy.” Gottlieb said.

The strongly worded remarks surprised meeting attendees and spurred new accusations between leading members of the drug supply chain. Shares of top PBMs CVS Health Corp and Express Scripts subsequently fell 1.4% and 2.4% respectively. The group that represents PBMs, the Pharmaceutical Care Management Association (PCMA), responded in a statement that it's unfair to blame payers – who pay two-thirds of the cost of drug benefits – for seeking the lowest costs in a marketplace where they have no control over the prices drug-makers set. These include price hikes imposed by originator manufacturers ahead of expected competition, which in turn elevate the prices charges by biosimilar manufacturers. Speculation has now intensified over what steps the Trump administration may take to rein in drug costs. On a more positive note, a recent decision by United Healthcare to pass along full drug rebates to more than 7 million people in its fully insured plans drew praise from the commissioner, who also outlined the FDA’s own plans to encourage biosimilar adoption. These include a pledge to establish an ”efficient path” for the demonstration of interchangeability, develop a comprehensive biosimilar access plan, provide more education on biosimilars for prescribers and patients, harmonize development with overseas regulatory partners and review how the FDA can assist biosimilar developers conduct smaller, targeted trials to bring their products to market in a more cost-effective and timely manner. Meanwhile, insurers and payers must decide if they want to continue to benefit from profitable rebates, Scott Gottlieb stated, or ”help generate a vibrant biosimilar market that can help reset biologic pricing.”

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USA: White House economists and "New England Journal of Medicine" article focus on poor US biosimilar uptake

The White House’s Council of Economic Advisors (CEA) has released a White Paper entitled Reforming Biopharmaceutical Pricing at Home and Abroad. The paper highlights the fact that the Medicare Part D program “creates perverse incentives for plan sponsors and pharmacy benefit managers (PBMs) to generate formularies that favor high-price, high-rebate drugs” and that drug manufacturer discounts need to be shared with patients. It also suggests that, once the Food and Drug Administration (FDA) finalizes its guidance for demonstrating interchangeability and ensures this guidance is “relatively easy and inexpensive to adhere to”, this could spur interchangeable applications and approvals, resulting in more effective competition by biosimilars. However, the not-for-profit group Knowledge Economy International, commented that “the White House report ignores the most important measure, which is to mandate greater access to manufacturing know-how and materials [from originator manufacturers], in order to reduce the costs and time of entry for biosimilar competitors.”

Meanwhile, an article in the New England Journal of Medicine, by Richard G. Frank, a health economist at Harvard Medical School, has warned that, if biosimilars continue their current trajectory, they could fail to deliver on their promise to provide cost savings to the US health system. Frank points out that only an estimated $3.2 billion (3%) of US biologic drug spending is currently subject to competition from biosimilars and those that are available have shown disappointingly slow uptake. Among the contributory factors for this situation, he notes that:

• The FDA’s use of 4-letter suffixes appended to the names of biosimilars may imply to prescribers that there could be clinically meaningful differences between a biosimilar and its originator.

• The FDA’s requirements for an interchangeability designation are still not clear and this has held up potential applications for products eligible for pharmacy-level substitution, which could generate substantial savings.

• Medicare’s reimbursement policies for biosimilars are ‘at best neutral with respect to the choice of product on the basis of price’ rather than actively promoting price competition.

• Originator manufacturers remain secretive about manufacturing processes.

“If the impediments continue, important savings will probably be left on the table” the article concludes. Other commentators have noted, however, that interchangeability is not really a significant issue given the influence of payers and price on formulary selection and the lack of a pharmacy-level decision for most Medicare Part B drugs. They note that more major barriers are originator manufacturers’ contracting tactics with payers, intellectual property litigation, and deliberate hold-ups in providing access to originator product supplies for biosimilar research and development.

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USA: ACR focuses on financial aspects of biosimilar usage

The American College of Rheumatology (ACR) has updated its health policy statements for 2018, with biosimilars featuring prominently. In addition to reiterating its strong support for biosimilars (with the caveat that it opposes “forced” switching and pharmacist substitution without prescriber consultation), the ACR focuses on the need to ensure that potential savings from biosimilars become a reality. Specifically, it states that:

• Biologic usage should be reimbursed at the complex rate under Medicare Part B; in recent years, a growing number of contractors have stopped reimbursing at this rate without consulting with physicians (as required by law).

• Specialty insurance tiers for biologic medicines that require high patient cost-sharing should be restricted by federal, state, and local legislation – and caps on total annual out-of-pocket spending should also be considered.

• Since patient assistance programs for high-cost drugs may unintentionally reduce demand for lower-cost therapies, these programs should be paired with other measures to reduce drug list prices. However, the ACR supports increased access to patient assistance programs for Medicare Part D beneficiaries and will support legislation that would allow Part B and Part D beneficiaries to receive financial co-pay assistance as part of such programs. The ACR also opposes insurance restrictions preventing the application of funds from assistance programs to patients’ deductibles and out-of-pocket minimums.

• New legislation should be introduced to allow Medicare to negotiate directly with pharmaceutical companies to achieve more affordable pricing of drugs.

• Greater transparency overall in how drug companies, pharmacy benefit managers, and payers determine the costs of medicines is warranted.

The ACR has also published a new White Paper, “The Science Behind Biosimilars — Entering a New Era of Biologic Therapy,” which shares the organization’s stance that it is reasonable for physicians to begin integrating biosimilars within patient care, where appropriate.

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USA: ASCO issues new statement on biosimilars

The American Society of Clinical Oncology (ASCO) has released a new statement that seeks to offer clinicians guidance on the use of biosimilars in oncology. The statement highlights:

• The important role of post-marketing evidence to demonstrate the value of biosimilars to stakeholders. However, it notes that current capabilities for post-market surveillance have shortcomings, and the Food and Drug Administration’s (FDA’s) Sentinel system is still in development. ASCO’s own big data candidate, CancerLinQTM, has potential value in tracking biosimilar use and effectiveness, according to the paper.

• The need for prescriber consultation and patient notification prior to any proposed biosimilar switch – even for biosimilar products which may in the future gain interchangeability status.

• The importance of prescriber and patient education on biosimilars. ASCO adds that practice guidelines for biosimilars will be an important part of oncologists’ education and points to the potential to develop webcasts, online practice guides, and social media updates via ASCO University. Patient-focused educational materials may also be developed for ASCO’s website and Meeting Library. However, the paper notes that “for patients, the best source of patient education is the treating physician, regardless of the prescribed drug.”

• The need for new policies that limit patients’ out-of-pocket costs and extend access to biologic therapy, while ensuring the delivery of quality care.

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USA: Sandoz’s ErelziTM (biosimilar etanercept) loses two indications at manufacturer’s own request

The FDA has removed two indications (psoriatic arthritis and plaque psoriasis) from the label of ErelziTM (etanercept-szzs) – a licensed but not-yet-marketed biosimilar of Amgen’s Enbrel® – at the request of the product’s own manufacturer Sandoz. The move appears to be a defensive tactic against patent infringement claims brought by Amgen, although neither Sandoz or Amgen were prepared to confirm this. The Food and Drug Administration (FDA) confirmed that the deletions were made at the sponsor’s request but declined to comment further. According to a legal observer, post-approval removal of indications due to patent or exclusivity issues is unusual; indications anticipated to be problematic from this perspective are usually trimmed ahead of filing or during the approval process. A court ruling on whether Sandoz can defend against infringement claims by carving out two of the biosimilar's five approved indications could have legal and regulatory ramifications for other biosimilar developers and originator product sponsors in the future.

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CANADA: CADTH revises biosimilar submission procedures

The Canadian Agency for Drugs and Technologies in Health (CADTH), the entity responsible for health technology assessments, has announced revisions to its approach to reviewing biosimilars. The new guidelines, effective as of February 13, 2018, include the following key changes:

• Shorter timeline: the timeline for review is reduced to three months from the current six months.

• Fewer submission requirements: the previous biosimilar submission templates have been abbreviated to reduce submission requirements.

• New fee structure: biosimilar submissions are subject to the new Guidelines for Manufacturers on Application Fees for CADTH Pharmaceutical Reviews.

• No reimbursement recommendations: CADTH will not issue reimbursement recommendations. However, it will review manufacturer-completed templates, provide a summary of stakeholder input and comment on the manufacturer’s cost-comparison table This information will be sent to the applicant and to participating drug plans and will be available on the CADTH website.

According to CADTH, these changes are intended to reduce duplication, optimize resources, and ensure all participating jurisdictions benefit from a single approach to reviewing submissions, which will allow faster inclusion of biosimilars in the individual Canadian provinces’ health plans.

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EUROPE: European Commission approves a second trastuzumab biosimilar, as the first launches in UK

The European Commission (EC) has granted a marketing authorization for Herzuma®, Celltrion’s trastuzumab biosimilar, for the treatment of HER2-positive early breast cancer, metastatic breast cancer, and metastatic gastric cancer. The approval of Herzuma® comes three months after fellow South Korean rival Samsung Bioepis received regulatory approval for Europe’s first trastuzumab biosimilar, Ontruzant®, in November 2017. Celltrion has indicated that intravenous Herzuma® could be launched at as much as a 50% discount to the subcutaneous formulation of Roche’s Herceptin®. Meanwhile, March 2018 saw the first EU launch of Ontruzant®, in the United Kingdom. A National Health Service (NHS) spokesperson welcomed this development, commenting: “The introduction of biosimilar trastuzumab provides an opportunity for the NHS to realise substantial financial savings without compromising patient care. Close collaboration between oncologists, pharmacists and nursing staff is required to ensure a seamless introduction into routine clinical practice.”

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March 2018   +

GLOBAL: New publications suggest Samsung’s etanercept and trastuzumab biosimilars may outshine their originators

A recent analysis of Phase 3 trial data, published in the British Journal of Dermatology, reports that Samsung Bioepis’s etanercept biosimilar, SB4 (approved as Benepali® in the European Union and Brenzys® in South Korea, Canada, and Australia), is associated with fewer injection-site reactions and less immunogenicity than originator etanercept (Enbrel®), while demonstrating equivalent efficacy. The authors of the article include clinicians from the US, UK, and Italy, as well as Samsung researchers. Shortly afterwards, data from Samsung’s Phase 3 comparison of its trastuzumab biosimilar (SB3) vs the originator Herceptin® in early stage breast cancer (neoadjuvant setting; n=800) appeared in the Journal of Clinical Oncology. The study showed that biosimilarity was demonstrated, but also pointed out that, in numerical terms, the primary endpoint of breast pathologic complete response (bpCR) was achieved in 10% more cases with SB3 than with Herceptin® (51.7% vs 42%). SB3 has already been approved in the EU and is currently being reviewed by the US Food and Drug Administration (FDA).

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GLOBAL: Disconnect between physicians’ expectations and feasibility in bioequivalence studies

To better understand physicians’ perceptions of the clinical meaningfulness of biosimilar trial results, a research team from Argentina has conducted an online survey of members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). Most respondents considered that ±5% would represent a clinically important difference between a biosimilar and an originator in terms of pharmacokinetics and efficacy – and even less for safety and immunogenicity. The authors highlight a disconnect between this perception and what is feasible to demonstrate statistically in practice. They observe that results of bioequivalence studies of infliximab biosimilars in immune-mediated diseases (which have led to approval for IBD indications by extrapolation) have used an equivalence margin of ±15%. Achieving a more sensitive margin than this would require much larger trial populations, which would be “difficult to impossible” to recruit, especially in rarer conditions. The survey findings have implications for educational efforts aimed at clinicians in relevant fields.

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EUROPE: New efforts to encourage biosimilar use in Finland, Switzerland, and France

Three European countries have announced new national plans intended to create better conditions for biosimilar uptake:

• The Finnish Medicines Agency (Fimea) has announced the launch of a study to investigate factors that promote or prevent the uptake of biosimilars. As part of the study, interviews will be conducted with prescribers of biologics across a range of therapy areas, as well as with patients. Fimea expects to publish the study’s results in 2019 and says the data should inform “pharmaco-political decision-making.”

• The Swiss Agency for Therapeutic Products (Swissmedic) has updated its guidance on the use of comparator products used in biosimilar trials. Previously, the only acceptable comparator products for pivotal studies were those authorized in Switzerland or the EU. In its updated guidance, Swissmedic says that comparator products can now originate from the US, and for supplementary studies, Canadian products will be allowed.

• France has committed to increasing biosimilar penetration to 80% by 2022 in its newly published health strategy plan (a 10% increase on last year’s target numbers). In addition to recommending biosimilars for all new patients, the plan also encourages switching to biosimilars (where available) for patients already receiving biologic therapies.

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EUROPE: Bevacizumab biosimilar approved in EU

Amgen and Allergan’s biosimilar of bevacizumab – which was approved by the US Food and Drug Administration (FDA) in September 2017 – has now also been approved in the EU. The licence for the biosimilar (marketed as Mvasi™) covers six cancer types including colon, rectum, breast, and lung cancer, but there could be a 4-year wait before the drug makes it to the market. The patent protecting the originator product, Roche’s Avastin®, expires in 2022, and there is no word yet from Amgen or Allergan about whether they plan to challenge it. However, it is possible the launch could come earlier should the companies find any weaknesses in the legal protection surrounding Avastin®.

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EUROPE: NHS England uses multi-stakeholder approach to achieve its biosimilars ambition

In November 2017, the National Health Service (NHS) governing body in England published new recommendations stating that at least 90% of new patients and at least 80% of existing patients should be prescribed the “best value biological medicine within 3 months of launch of a biosimilar medicine,” with the aim of delivering annual savings of £200m – £300m by 2020/21. It’s now been revealed that this new commissioning framework was developed via a multi-stakeholder process, which recognized that biosimilar uptake has numerous drivers and barriers, reflecting much more than just the price tag of a product. A committee called the National Biosimilars Medicines Programme Board (NBMPB) was set up to bring together all stakeholders, including the British Biosimilars Association (BBA), the Association of the British Pharmaceutical Industry (ABPI), clinicians, patient advocacy groups, the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) and the National Institute for Heath and Care Excellence (NICE). The commissioning policy was formulated once the views of all these stakeholders had been taken into account. Separately, four Regional Medicines Optimization Committees (RMOCs) were set up to monitor the extent to which hospital trusts and commissioning groups in their regions are following the National Commissioning Guidelines. According to NHS England, the true potential of biosimilars will only be realized if they are embraced across the country in a “proactive, systematic, and safe way.”

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EUROPE: UK regulator seeks to reassure pharma industry as Brexit nears

In an update to pharmaceutical companies on preparations for Brexit, the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) reassured industry that “goods placed on the market under Union law before the withdrawal date may freely circulate in the UK and EU markets with no need for product modifications or re-labelling.” MHRA also notes that it is seeking to negotiate an implementation period that would enable cooperation between the UK and EU markets to continue temporarily on current terms. However, the agency acknowledged the possibility that, ultimately, the UK may not be able to have a continued relationship with the European Medicines Agency (EMA). In the event of such a “no-deal” outcome, the MHRA plans to convert the existing EU legislative framework into UK law at the time of exit so that there will be no sudden changes to UK regulation. When the changes do eventually come, “pragmatic” adjustments to regulatory requirements would be rolled out with adequate notice to ensure that companies have enough time to implement the new requirements.

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USA: House of representatives passes budget bill with implications for market access to biosimilars

The US House of Representatives has passed a budget bill including two provisions with implications for market access to biosimilars. First, the draft continuing resolution seeks to add biosimilars to the Medicare Part D coverage gap – or “donut hole” – discount program. This program requires drug manufacturers to provide discounts to Medicare beneficiaries when their costs exceed the Part D initial coverage limit but are less than the threshold for catastrophic coverage. Adding biosimilars to the Part D coverage gap discount program will ensure that biosimilars are included in formularies and may achieve government savings of around $1 billion over 10 years, according to the Association for Accessible Medicines (AAM). However, the second provision in the bill excludes biosimilars from the Part B “pass-through” payment program.

The pass-through payment provides higher reimbursement levels for a 3-year period to new drugs and devices that are administered in hospital out-patient facilities or physicians’ offices. Christine Simmon, Executive Director of the Biosimilars Council and Senior Vice President of Policy for AAM, commented “On the one hand, the House of Representatives pursues a goal we support – increasing patient access to life-saving medicines by placing biosimilars and high-priced brands on a level playing field in Medicare Part D. At the same time, however, the continuing resolution would place biosimilars at a significant disadvantage in outpatient settings, undermining the opportunity for physician adoption. If the goal is to create a robust biosimilars market in the US, we encourage Congress to ensure that biosimilars and high-priced brands are treated equally across all settings of care.” The bill now moves to the US Senate.

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USA: American College of Rheumatology recommends biosimilar use in new White Paper

The American College of Rheumatology (ACR) has published a new White Paper, “The Science Behind Biosimilars – Entering a New Era of Biologic Therapy,” providing a comprehensive overview of the scientific, clinical, economic, and prescribing issues pertaining to biosimilar use, including efficacy, competition, and drug pricing. The paper encourages providers to incorporate these drugs into treatment plans of patients with rheumatic diseases where appropriate.

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ASIA PACIFIC: Australian government announces decision on biosimilar naming

Australia’s Therapeutic Goods Administration (TGA) has confirmed that it will not adopt the US Food and Drug Administration’s (FDA’s) approach of using 4-letter suffixes in naming biologic and biosimilar medicines, but will maintain its current system of using the biologic name without a specific identifier. The decision aligns with the nomenclature policies favored by the EU and the World Health Organization (WHO). The TGA’s position includes a future possible move toward adopting the EU’s barcode system, which incorporates the product code, national identification number, batch number, and expiry date. To support pharmacovigilance, the TGA also announced a plan to make products’ brand names (as well as non-proprietary names) a mandatory field when reporting an adverse event.

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LATIN AMERICA: Brazilian Society of Clinical Oncology issues biosimilars position paper

The Brazilian Society of Clinical Oncology (SBOC) has released its official position on the use of biosimilars in oncology. As of February 2018, only two oncology biosimilars (filgrastim and trastuzumab) have been approved for use in Brazil, though the number of applications filed with the National Health Surveillance Agency (ANVISA) is expected to grow steadily in the coming years. Within its position statement SBOC recognizes that, while survival outcomes are important in clinical trials of new originator biologics, other endpoints, such as pathological complete response or progression-free survival are appropriate for pivotal trials of oncology biosimilars. The SBOC accepts the concepts of interchangeability and extrapolation of indications, but calls for robust evidence on a case-by-case basis to support these practices. In addition, the SBOC advocates rigorous pharmacovigilance, education for healthcare providers on biosimilars, and global harmonization of regulatory requirements. In concluding its position, the SBOC said that it “…takes a stand in favor of biosimilars,” and that it hopes its position can provide valuable information to support therapeutic decisions that maximize clinical benefit for patients and expedite the introduction of biosimilars into clinical practice.

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February 2018   +

GLOBAL: Novartis takes on Humira® – and their own prospective adalimumab biosimilar – in head-to-head superiority trials with Cosentyx®

Novartis has announced the launch of the SURPASS Study, a head-to-head superiority trial of secukinumab (Cosentyx®) versus their own proposed biosimilar of adalimumab, in patients with ankylosing spondylitis. The SURPASS Study is part of a larger clinical program for secukinumab, which includes the EXCEED Study, a head-to-head superiority trial of secukinumab versus Humira® itself (originator adalimumab) in patients with psoriatic arthritis. Announcement of the SURPASS Study follows the release of November 2017 data confirming the lack of clinically meaningful differences in patients who switched back and forth between Humira® and Novartis' adalimumab biosimilar multiple times, and those patients who stayed on the biosimilar throughout the study. Despite the potential of their adalimumab biosimilar to eventually capture a share of Humira's® market, Novartis has clearly decided to prioritize Cosentyx®, which has already become a top-seller since its launch in 2015. The intention behind the EXCEED and SURPASS Studies seems to be to demonstrate that not only is Cosentyx® clinically superior to Humira® itself, but is also sufficiently superior to lower-priced adalimumab biosimilars that their cost savings cannot be justified. This is the first time a biosimilar has been used as a comparator in a major study versus a different originator.

The news of Novartis' attempt to directly challenge Humira® comes just after AbbVie's announcement of a 9.7% price rise for Humira®, which has more than doubled in price since 2012. According to one analyst, the latest price increase could add $1.2 billion to the US healthcare system's drug costs in 2018, especially since AbbVie has used patent litigation to prevent adalimumab biosimilars from reaching the market before 2023.

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GLOBAL: Race to a pegfilgrastim biosimilar picks up again

Sandoz has announced results from a new Phase 1 crossover study showing that its proposed pegfilgrastim biosimilar (LA-EP2006) matches the originator, Amgen's Neulasta®, in terms of safety, pharmacokinetics, pharmacodynamics, and immunogenicity in healthy volunteers. The data were presented at the San Antonio Breast Cancer Symposium in December 2017. The US Food and Drug Administration (FDA) had originally rejected Sandoz's pegfilgrastim biosimilar in July 2016, issuing a Complete Response Letter (CRL). The European Medicines Agency's (EMA's) review of LA-EP2006 is still underway, but Sandoz claims these new data add to the totality of evidence in support of the product. There are no pegfilgrastim biosimilars approved at present in either the US or Europe. Biocon withdrew its EMA application for its prospective pegfilgrastim biosimilar following an FDA CRL (as well as concerns from European regulators) regarding the quality of its manufacturing plant in Bangalore, India, but it since claims to have addressed these concerns and resubmitted its EMA application in November 2017. Meanwhile, the EMA has also accepted Mumbai-based pharmaceutical company USV Pvt Ltd's marketing application for a pegfilgrastim biosimilar.

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USA: Federal Circuit says state laws can’t be used to impose 180-day notice period prior to a biosimilar launch

The US Court of Appeals for the Federal Circuit (CAFC) has decided a key remaining question in the long-standing legal battle between Amgen and Sandoz over whether a biosimilar maker ever needs to give the originator manufacturer 180 days' notice of its intention to launch following FDA approval. The original case was escalated to the Supreme Court, which ruled, in June 2017, that Sandoz was not obliged to wait an additional 180 days after licensing before its biosimilar product Zarxio™ could be commercialized. Amgen then sought to leverage individual state laws to impose this notice period at a local level – but the CAFC has now confirmed that Sandoz cannot be compelled under any state law to give Amgen 180 days' notice of launching Zarxio™, and that state laws cannot preempt federal laws in this instance. Alan Clement, Chair of the Intellectual Property Department at the law firm Locke Lord, observed that, following the Supreme Court ruling, "the CAFC has closed the door on what remedies remained available to a brand biologic company in terms of a biosimilar applicant who is refusing to engage in the 'patent dance' under the BPCIA." A Sandoz spokesperson added: "While reference medicine manufacturers will no doubt try and continue to use the legal system to create unnecessary and costly barriers that delay biosimilar approval or availability, this is one of several wins this year that prove the tide is turning for broad-based biosimilar access."

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USA: FDA approves Sanofi's Admelog® as a follow-on biologic of insulin lispro

The US Food and Drug Administration (FDA) has granted final approval to its first short-acting follow-on insulin product, Sanofi's Admelog® (insulin lispro injection). Final approval of the drug follows the FDA's tentative approval, granted in September 2017. The agency could not issue its final approval until the resolution of patent disputes with Eli Lilly, the manufacturer of the originator product Humalog®. Because the FDA treats originator insulins as drugs, rather than as biologic products, treatments such as Admelog® are approved through the 505(b)(2) pathway as "follow-ons," not via the 351k pathway as biosimilars. This differs from the situation in Europe where Admelog® is approved by the European Medicines Agency (EMA) as a biosimilar insulin. However, in 2020, products like insulin will all be transitioned to biologics and their "follow-on" versions will then be regulated by the FDA as biosimilars.

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USA: FDA approves a second Pfizer infliximab biosimilar – but there are no plans for its launch

The US Food and Drug Administration (FDA) has approved Pfizer's second biosimilar of infliximab, Ixifi™, for all eligible indications of Johnson & Johnson's originator Remicade®. This puts Pfizer in the unusual position of owning two FDA-approved infliximab biosimilars, although the other one – Inflectra® – is in partnership with Celltrion. Pfizer acquired Inflectra® when it bought Illinois-based Hospira in 2015. At the time, Pfizer elected not to discontinue development of Ixifi™, which was already underway, but now says it has no plans to commercialize the product in the US – where the company is already heavily investing in Inflectra® – or in Europe, where it has already sold marketing rights to Sandoz. "We are currently evaluating our strategic options for Ixifi™," a Pfizer spokesman said.

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EUROPE: Prescriber survey reveals lack of knowledge about variability of originator biologic drugs

A survey conducted among a sample of Spanish physicians specializing in rheumatology, gastroenterology, and dermatology has revealed a notable lack of knowledge about the fact that licensed originator biologic drugs typically undergo several changes to their manufacturing process, which may affect the quality attributes of the product in potentially clinically meaningful ways. Such knowledge is important to minimize potential distrust of biosimilars among prescribers, who may not realize that originator biologics are inherently variable, and there can be as much difference between an originator biologic before and after major manufacturing changes as there is between a biologic and its biosimilar. Some 63% of respondents were not aware that such manufacturing modifications occur. The remainder were aware – but had little idea how frequently such modifications occur (for example, there have been over 40 for Remicade® and 20 for Humira® since they received a license from the European Medicines Agency [EMA]). In addition, more than 50% of respondents were unaware of the EMA requirement for comparability data in the wake of a manufacturing change, which is akin to some of the data biosimilar developers are expected to submit. While the survey was small (n=35), the authors concluded that educating physicians about these matters may help to contextualize their perception of biosimilars, increase confidence, and improve uptake.

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EUROPE: EMA issues guidance on impact of Brexit for biosimilar manufacturers

The European Medicines Agency (EMA) has published guidance for biosimilar makers in light of Brexit (the impending departure of the UK from the European Union). Among the considerations addressed are the fact that, once Brexit comes into force on March 30, 2019, all biosimilar applications to the EMA should refer to an originator comparator product authorized in one of the 27 remaining EU Member States or a European Economic Area (EEA) State. Batches of a reference product released by the UK as of March 30, 2019 will not be considered an EEA authorized comparator.

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January 2018   +

GLOBAL: FDA and EMA both approve their first trastuzumab biosimilar

In a major development for the use of biosimilars in oncology, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have both approved their first biosimilar of trastuzumab, based on Roche’s Herceptin®. In the case of the EMA, it is Samsung Bioepis’ Ontruzant® that has gained the first trastuzumab approval in Europe, while in the United States it is Mylan and Biocon’s Ogivri (which has been given the non-proprietary name trastuzumab-dkst). Proposed launch dates and market prices have yet to be announced. Roche is claiming patent protection for Herceptin® in the US until 2019, but its EU patents expired in 2014.

For further details about each of these approvals, please see the following "Industry News" stories further down this page:
Europe: EMA approves its first trastuzumab biosimilar
USA: FDA approves its first trastuzumab biosimilar

Herceptin® has become standard of care in both early and metastatic HER2-postive breast cancer, significantly improving the survival of these patients. However, the cost of 12 months of adjuvant Herceptin® therapy (the standard duration of treatment), as well as the cost of indefinite use in a metastatic setting, limits patient access to this life-saving drug. For example, a study published in Lancet Oncology showed that, currently, only one-third of HER2-positive breast cancer patients in China have access to Herceptin®. According to an editorial by Arlene Chan in Chinese Clinical Oncology, it remains to be seen whether the availability of trastuzumab biosimilars can translate into greater utilization of this targeted therapy, especially for those who do not currently receive it. As more biosimilars enter the clinical setting for breast cancer and HER2-positive solid tumors, it will be important not only to demonstrate the cost savings that are achieved by healthcare providers, but also to collect institutional and national data showing that more patients are actually receiving this therapy.

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GLOBAL: Sandoz and Celltrion report new data at the 2017 ACR Annual Meeting

Delegates at the American College of Rheumatology (ACR) Annual Meeting in San Diego, California, heard Sandoz present 24-week results from the EQUIRA Study, a phase 3 trial comparing their etanercept biosimilar Erelzi (etanercept-szzs) with the originator Enbrel® in 326 patients with moderate-to-severe rheumatoid arthritis (RA) who had had an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs). The study confirmed the comparable safety and efficacy of Erelzi and Enbrel® at 24 weeks. Erelzi was approved by the US Food and Drug Administration (FDA) in August 2016 and by the European Medicines Agency (EMA) in July 2017, for use in all indications of Enbrel® at the time of approval. Sandoz also presented data from four clinical studies on their proposed biosimilars of adalimumab (currently under EMA review) and rituximab (already EMA-approved and under FDA review). The efficacy and safety of their biosimilar adalimumab and the safety of their biosimilar rituximab were shown to match the originators in multiple-switching and re-treatment studies, respectively. Studies included two innovative trials involving switching and two pharmacokinetic and pharmacodynamic studies.

Meanwhile, ACR delegates also heard Celltrion report results of a switching study (n=295) with their rituximab biosimilar Truxima®. After 48 weeks’ initial treatment with Truxima® or the originator Rituxan®, patients who had received Rituxan® were either maintained or were switched to Truxima® and observed for a further 24 weeks. Equivalent efficacy and similar pharmacokinetic and safety profiles were demonstrated in those who had switched to Truxima® or remained on Rituxan®. In April, Celltrion launched Truxima® in Europe as the first EMA-approved rituximab biosimilar. Truxima® is pending FDA review.

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GLOBAL: ASH Annual Meeting hears how savings from biosimilar filgrastim can expand access to other high-cost drugs

Results of a study showing how expanded access to the drug obinutuzumab (Gazyva®) was made possible on a budget-neutral basis through savings obtained from using biosimilar filgrastim-sndz (Zarxio®) were presented at the American Society of Hematology (ASH) 59th Annual Meeting in Atlanta, Georgia. The study estimated the savings achievable from converting febrile neutropenia prophylaxis from originator filgrastim (Neupogen®) or pegfilgrastim (Neulasta®) to Zarxio® and simulated a hypothetical reallocation of those savings to therapeutic care with obinutuzumab (a humanized anti-CD20 monoclonal antibody approved in 2016 for relapsed or refractory follicular lymphoma). Using the assumption of therapeutic similarity between filgrastim, pegfilgrastim, and biosimilar filgrastim, the study found that conversion to biosimilar filgrastim for 20,000 patients could provide expanded access to obinutuzumab for the following number of patients:

Additional patients who could be treated with obinutuzumab at no extra cost

Use of biosimilar filgrastim in 20,000 patients Prophylaxis regimen
5-day 7-day 11-day 14-day
Conversion from originator filgrastim 60 85 133 169
Conversion from originator pegfilgrastim* 516 435 275 154

*Conversion-related savings relative to pegfilgrastim decline as daily injections increase.

The study results show that conversion to biosimilar filgrastim (especially from pegfilgrastim) for febrile neutropenia prophylaxis in large patient populations can enable more patients with hematologic malignancies to receive cutting-edge therapy at no additional cost to payers.

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GLOBAL: Speculation about the “nocebo effect” intensifies

The “nocebo” effect – a phenomenon that occurs when a patient’s negative perception of a therapy causes it to have a worse outcome than would otherwise be expected – has become a topic of increasing interest in the world of biosimilars as some patients begin to transition from familiar, high-cost biologics to new, lower-cost biosimilars. In a recent Dutch study, which reported a 24% discontinuation rate at 6 months for patients transitioned from Remicade® to biosimilar infliximab, the researchers blamed the nocebo effect, calling the reasons for discontinuing the biosimilar “subjective.” Research presented at the American College of Rheumatology’s 2017 Annual Meeting found that careful counseling of patients about proposed switches appears to be an effective way to counter the nocebo effect. However, industry stakeholders are becoming concerned about how frequently this issue is now arising – and not everyone agrees that the nocebo effect adequately explains the phenomenon of patients discontinuing biosimilar therapy. For example, a case study, newly published in the European Journal of Rheumatology, highlighted three patients with Behçet’s disease for whom a switch to biosimilar infliximab during routine clinical practice was associated with a rapid loss of treatment efficacy. All three patients required treatment with a different anti-TNF, adalimumab, to regain clinical remission.

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USA: FDA approves its first trastuzumab biosimilar

The US Food and Drug Administration (FDA) today approved Mylan’s Ogivri® (trastuzumab-dkst) as a biosimilar to Herceptin® (trastuzumab) for the treatment of patients with early or metastatic breast cancer or metastatic stomach cancer whose tumors over-express the HER2 gene (HER2+). The approval of Ogivri® – the first trastuzumab biosimilar approved in the US – comes after an FDA advisory panel unanimously backed its approval for all eligible indications of Herceptin®, based on a submission package that included results from the phase 3 Heritage Study. The FDA approval of Ogivri® was subject to a 3-month delay while the FDA sought “clarification” on certain aspects of the submission. Mylan has confirmed that this delay was unrelated to issues that were also raised by the FDA about quality compliance at the manufacturing plant where the drug is produced. Similar issues raised by the European Medicines Agency (EMA) about the plant had caused Mylan to withdraw its European application for Ogivri®, but a re-submission is likely now that these issues have been resolved. Mylan – who developed Ogivri® in partnership with Biocon – reached a global agreement with Roche earlier this year concerning patents covering Herceptin®. This agreement does not extend to other manufacturers, as Roche is claiming patent protection for Herceptin® until 2019 in the US and is pursuing patent infringement litigation against Pfizer, who has a trastuzumab biosimilar currently undergoing FDA review.

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USA: Leading US rheumatologists engage in the “Great Debate: ACR 2017 – to Switch or NOT to Switch?”

At this year’s American College of Rheumatology (ACR) 2017 Annual Meeting in San Diego, California, “The Great Debate: Biosimilars…to Switch, or Not to Switch? That is the Question” was among the most highly anticipated events of the conference. With Jonathan Kay, MD, arguing in favor of switching patients to biosimilars and Roy Fleischmann, MD, arguing against, the debate seemed primed to be a discussion of the growing body of evidence concerning the safety, efficacy, and potential cost benefits of switching patients to biosimilar therapies.

Kay reviewed the findings of NOR-SWITCH and other key studies on biosimilar switching and discussed the so-called “nocebo” effect in explaining why some studies show patients switching back to originator drugs after having moved to biosimilars. He emphasized that any risk associated with a switch to a biosimilar should be weighed against potential benefits for all patients; biosimilars should decrease the cost of treatment, introduce market competition, and create access for patients who need biologic therapy. In opposition, Fleischmann’s primary focus was on the cost savings promised by biosimilars, which have not yet been delivered in the US marketplace. He pointed out that, while the European experience has demonstrated significant cost savings with biosimilars, which have in turn benefitted patients, single-payer systems like those in Europe have the opportunity to drive hard bargains with drugmakers. In the US, however, insurance plans typically contract with pharmacy benefit managers (PBMs) to negotiate drug prices with pharma, while patients themselves do not reap the benefits of any savings. Fleischmann asserted that, at present, 58% of health plans do not reimburse for biosimilar infliximab, forcing patients to receive (and pay their copays on) the higher-cost originator drug. He also highlighted AbbVie’s recent settlement with Amgen over Humira®, which “…suggests that the industry’s long-standing strategy of using patents to ward off cheaper competition for brand-name drugs is extending into the era of biosimilars. So when is Humira® going to be cheaper for patients?” Currently, the only side of the biosimilar equation achieving a benefit, he indicated, is the payer.

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USA: Industry stakeholders comment on FDA draft guidance for evaluating biosimilarity

On December 4, 2017, a final round of comments from industry stakeholders who raised questions over US Food and Drug Administration’s (FDA’s) draft guidance, “Statistical Approaches to Evaluate Analytical Similarity,” was published on the website The latest draft guidance, announced in September 2017, describes the type of information that sponsors should obtain regarding the structural/physicochemical and functional attributes of the originator product and how to utilize that information in their biosimilar R&D plans. Among those who commented were Amgen, Boehringer Ingelheim, Genentech, Novartis, Pfizer, Sanofi, and Shire. Other industry stakeholders included the Association for Accessible Medicines (AAM), the Biosimilars Forum, and the Biotechnology Innovation Organization (BIO). Points raised in the feedback included:

  • The appropriate role of statistical analyses to evaluate analytical similarity data.
  • The challenge of determining an appropriate biologically or clinically meaningful margin for equivalence testing.
  • The need for scientific and regulatory consistency for all biologics, not only biosimilars.
  • The need to recognize that a critical element for evaluating similarity is prior knowledge of all biologics (such as understanding quality attributes, understanding the molecular basis of the disease a biologic is meant to treat, and understanding the dynamics of vulnerable populations).
  • The need to keep the concepts of physical/chemical attributes separate from the concept of biological functions to accommodate sponsors who take these two different approaches to defining a biosimilar product’s quality attributes.
  • The concern that biosimilar developers have no control over the quality attributes of the reference product.
  • The need to develop a protocol for both the statistical methods and experimental design to ensure rigorous assessment.
  • The need for the FDA to be prepared to facilitate discussion early in the biosimilar development process to minimize misinterpretation of expectations.

The FDA is now in the process of considering the feedback received.

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USA: FDA Commissioner announces draft REMS guidance to avoid delays to biosimilar development

Scott Gottlieb, MD, Commissioner of the US Food and Drug Administration (FDA), has called on drugmakers to “end the shenanigans” that delay drug competition in the US marketplace. Gottlieb’s comment was made at the same time as a statement announcing new FDA draft guidance on streamlining the submission and review process for shared-system risk evaluation and mitigation strategies (REMS) programs. While REMS are designed to protect patient safety by providing such materials as medication guides or package inserts (requiring activities like provider training and patient counseling in some cases), REMS have come under fire as a way for makers of innovator drugs to stave off competition from generics and biosimilars. Because originator product manufacturers and biosimilar or generic drug developers must agree on a single, shared REMS system, the need for such negotiations can potentially be abused to delay the market entry of cheaper drugs. “[We] need to make sure that REMS programs maintain their role in serving public health and don’t become a tool companies can use to delay or block competition from generic products entering the market,” Gottlieb said, announcing new FDA draft guidance for industry that describes how applicants can submit drug master files, representing all participating firms, to the agency. The draft guidance eliminates the need for each manufacturer involved in a REMS process to submit files individually, eliminates duplicative paperwork for drug makers, and streamlines the forms that the FDA’s reviewers must assess. While the new drug master file system is not mandatory, Gottlieb said that “we strongly encourage” its use.

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EUROPE: EMA approves its first trastuzumab biosimilar

The European Medicines Agency (EMA) has approved its first trastuzumab biosimilar – Samsung Bioepis’ Ontruzant® – for the full range of registered indications of the originator Herceptin®, including early breast cancer, metastatic breast cancer and metastatic gastric cancer. Ontruzant® will be commercialized across Europe by MSD (known as Merck & Co in the US and Canada). Launch dates and pricing plans have not yet been revealed but, as Roche’s patent for Herceptin® expired in Europe in 2014, potential stumbling blocks might come in the shape of market access issues in individual countries. As the first biosimilar monoclonal antibody solely for use in oncology, the licensing of Ontruzant® represents a new milestone for biosimilars and has been eagerly anticipated by the oncology community.

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EUROPE: EMA approves its third adalimumab biosimilar

A third adalimumab biosimilar – Boehringer Ingelheim’s Cyltezo® – has been approved by the European Medicines Agency (EMA). Cyltezo®, which gained US Food and Drug Administration (FDA) approval a few months previously, has been approved for a wide range of the indications of the originator, AbbVie’s Humira®, in adults and children. The data package submitted included results from the pivotal phase 3 study VOLTAIRE®-RA. Although the main EU patent for Humira® expires in October 2018, AbbVie is likely to delay the launch of adalimumab biosimilars in Europe by claiming infringement of various other patents. The exception will be Amgevita – the first EMA-approved adalimumab biosimilar developed by Amgen, with whom AbbVie has reached a legal settlement.

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EUROPE: European Commission launches patient Q&A on biosimilars in 23 languages

The European Commission (EC) has launched a comprehensive patient-focused question-and-answer document, entitled “What I Need to Know About Biosimilar Medicines,” translated into 23 EU languages. The information – which was compiled with the input of a range of stakeholders, including patient organizations – is intended to provide patients with unbiased, reliable information on biosimilar therapies, including clinical, regulatory, governmental and health economic aspects. Links to other patient-friendly sources of information are also provided. Looking ahead to 2018, the EC anticipates that its biosimilar information guide for healthcare professionals will be available in six additional EU languages in the first half of the year. A stakeholder workshop on biosimilars is also planned for September 2018, focusing on oncology, public procurement, and the role of nurses and pharmacists in spurring biosimilar uptake.

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EUROPE: UK’s NHS launches new biosimilars website for patients, healthcare professionals, and industry

The UK’s National Institute for Health Research (NIHR), part of the National Health Service (NHS), has launched a major new website Focus on biosimilars, claiming that biosimilars “may well hold the key to ensuring the sustainability of our globally renowned public healthcare system.” The website consists of three portals, one for biotech companies, one for NHS healthcare professionals, and one for patients and caregivers. The patient portal features interviews, which explain typical patient experiences with biosimilars, what switching programs are, and how patients can benefit from participation in biosimilar clinical trials. The website points out that uptake and acceptance of biosimilars has rapidly accelerated across the NHS in recent years – but also discusses the difficulty of finding investigators for biosimilar clinical trials in key therapy areas, given that “the usual suspects” (i.e. the clinicians whom would normally be approached) prefer to be involved in trials of new innovator products. In response to this situation, the NIHR Clinical Research Network (CRN) has created biosimilar clinical trial “packages” that offer an alternative route to finding biosimilar study investigators and sites across the region. The new website can be accessed at:

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EUROPE: French government calls for 70% biosimilar prescribing rate

In a concerted effort to encourage the wider use of biosimilars nationally, the French Health Ministry has asked doctors to aim for a biosimilar prescribing rate of at least 70%, anticipating savings of €40m in 2018. Regional health agencies have been asked to take steps to reach these objectives, while keeping the ministry informed of their plans. In addition, to make it easier for pharmacists to substitute a biosimilar for a prescribed originator, a register of biologic medicine groups based on 11 originators has been set up. The register includes links to a database of excipients with known effects and, bearing in mind that originators and biosimilars may contain different excipients, healthcare professionals have been advised to take these into account when making a substitution. The rules on substitution in France, which have been in place since December 2016, allow pharmacists to substitute biosimilars within the relevant product group (either at the initiation of treatment or during the course of it) provided the prescriber has not written “not substitutable.”

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EUROPE: Medicines for Ireland claims that Irish patients are unfairly missing out on biosimilars

Medicines for Ireland, the association representing generic and biosimilar suppliers in the Republic of Ireland, has cautioned that a promised new National Biosimilars Policy may lead to no meaningful change in the accessibility of affordable biologic treatments for Irish patients. It highlights the current poor uptake of biosimilars, claiming that the key issue is the State’s own pricing agreement with the Irish pharmaceutical industry, which mandates a 30% drop in the price of an originator when a biosimilar enters the market. While this discount appears attractive at first, it essentially means biosimilar manufacturers have no incentive to compete. Ireland’s Department of Health completed a public consultation on biosimilars in September 2017 and Medicines for Ireland has now called on the Department to resist pressure from vested interests to maintain the status quo. According to Sandra Gannon, Joint Chairperson of Medicines for Ireland, “this ‘blocker clause’ is sending out the message to biosimilar companies that Ireland is closed for business.”

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ASIA PACIFIC: Australian “uptake drivers” for boosting biosimilar prescribing start with etanercept

The Australian government is taking further steps to boost the biosimilars market, this time in the form of "uptake drivers" that will be applied to individual medicines. These drivers are time-limited initiatives to help biosimilars gain acceptance among healthcare professionals. The first drivers, which relate to etanercept, were implemented on December 1, 2017. Samsung Bioepis’ biosimilar version of etanercept, Brenzys, was officially listed on the national Pharmaceutical Benefits Scheme (PBS) as an A-flagged product earlier this year, meaning that pharmacists may substitute it for the originator, Enbrel®, unless specifically notified by the prescriber not to do so. Biosimilar versions of infliximab (Inflectra® and Renflexis) are also A-flagged. Although prescribing biosimilars has not been made mandatory in Australia, prescribers will be reminded that “encouraging biosimilar prescribing for treatment-naïve patients is government policy and could result in reduced costs for biological medicines, allowing the government to reinvest in new treatments.”

Two drivers will be put in place for each product: (1) encouraging the prescribing of a biosimilar instead of the originator for treatment-naïve patients – which may in future involve changes to physicians’ prescribing software to provide hints and reminders; and (2) implementing a simpler, faster process for gaining approval to prescribe PBS-listed biosimilars (streamlined authority), while keeping the existing higher-level authority requirement for PBS-listed originators (written authority). Prescribers remain able to decide which product to prescribe, in consultation with patients, and can continue to tick the “no substitution” box.

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SUB-SAHARAN AFRICA: South Africa approves its first biosimilar

South Africa’s Medicines Control Council (MCC) has approved the country’s first biosimilar product – a biosimilar of filgrastim developed by Teva. This first biosimilar approval has been long awaited since the MCC issued regulatory guidelines for biosimilar developers (based on those of the European Medicines Agency) as far back as 2012. Some have criticized the country’s registration policy for creating a backlog and delaying access to many important medicines, including biosimilars. It has therefore been suggested that the MCC alter its strategy for handling applications from one that’s based on submission date to one that is based on the degree of public need for the product in question.

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December 2017   +

GLOBAL: Speculation about the “nocebo” effect with biosimilars increases

A new study published in Arthritis & Rheumatology reports that 24% of patients (n=192) who switched from Remicade® to an infliximab biosimilar (CT-P13) had discontinued treatment within 6 months primarily due to “subjective health complaints.” The authors attribute the CT-P13 discontinuation to a possible “nocebo” effect. Similar findings were obtained from a study of a nationwide switch from originator infliximab to a biosimilar in Denmark, in which the investigators reported that 16% of patients stopped treatment, even if disease activity seemed largely unaffected by the switch. The nocebo effect is a phenomenon that occurs when a patient’s negative expectation causes a treatment to perform less well than it otherwise would – essentially, the opposite of a placebo effect. The effect can be attributed to a patient’s perception that the biosimilar is inferior to the originator drug – a perception that may be inferred from comments made by prescribers about the need to prescribe a more affordable treatment. The way in which physicians communicate with patients about switching to a biosimilar is considered key to preventing the nocebo effect and helping to ensure the success of transitioning to biosimilars in daily practice.

Meanwhile, at the 2017 American College of Rheumatology’s (ACR) Annual Meeting in San Diego, CA, USA, four separate studies analyzed the reasons for successes and failures in non-medical switching initiatives (i.e. pharmacy-level substitution) concerning etanercept and infliximab biosimilars. Although non-medical switching has implications beyond switching that’s authorized by a prescriber, patient communication was again highlighted as a key driver of success or failure.

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GLOBAL: Boehringer Ingelheim’s adalimumab biosimilar shows promise after switching

Boehringer Ingelheim has announced 48-week data from a Phase 3 clinical trial comparing their adalimumab biosimilar Cyltezo® with Humira® in moderate-to-severe rheumatoid arthritis (RA). The data showed that Cyltezo® has no clinically meaningful differences in efficacy, safety, and immunogenicity to Humira®, even in patients who switched from Humira® to Cyltezo® at Week 24. Meanwhile – as it faces the prospect of oncoming biosimilar competition to Humira® – AbbVie is developing a new innovator product, which could help it retain a hold on the market. Results from three recent Phase 3 clinical trials show AbbVie’s investigational interleukin-23 (IL-23) inhibitor, risankizumab, to be more effective than adalimumab (Humira®) or ustekinumab (Stelara®) in patients with moderate-to-severe plaque psoriasis.

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GLOBAL: Global biosimilars market estimated to be worth over $13 billion by 2024

According to a new market research forecast from Hexa Research, the global biosimilars market is expected to reach $13.1 billion by 2024 as a result of a continued rise in the prevalence of cancer and chronic conditions, such as diabetes and autoimmune diseases.

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EUROPE: European Commission launches consultation on patent protection schemes and exemptions

The European Commission has launched a public consultation on supplementary protection certificates (SPCs) and related patent exemptions, which could have a significant impact on the biosimilars marketplace. SPCs are an intellectual property right that grants an extension of up to 5 years on a 20-year patent term for an innovative pharmaceutical. The goal of the SPC is to offset the loss of patent protection that occurs during the development and clinical trials of a generic product. Bolar patent exemptions, which are intended to speed market entry of generic and biosimilar therapies, provide exemptions to patent protection, even in cases where SPCs are in force. These exemptions state that some pre-market activities cannot be regarded as infringements of a patent or SPC. However, because SPCs are granted and enforced at a national level, rather than a European Union (EU) level, confusion about these certificates and their related Bolar exemptions is widespread. For example, in some EU member states, Bolar exemptions do not permit access to active pharmaceutical ingredients for the purpose of biosimilar development. Bolar exemptions have also been under scrutiny as they may prevent EU manufacturers from competing in non-EU markets during the SPC term. In addition, SPCs have been questioned in the biosimilars context due to the very nature of biosimilar therapies. Because SPCs cover the active ingredient in a product and because biosimilars are, by definition, only “highly similar” to their originators, there remains some question as to whether SPCs can be legitimately applied to forestall biosimilar development. The new consultation is intended to gain feedback from stakeholders in order to determine a future course of action by the European Commission.

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USA: CMS reverses its policy on biosimilar reimbursement

The Centers for Medicare & Medicaid Services (CMS) has announced a long-awaited change to its present policy on biosimilar reimbursement, stating that it will begin issuing unique Healthcare Common Procedure Coding System (HCPCS) codes (often referred to as “J-codes”) to each individual biosimilar product, beginning on or after January 1, 2018. Currently, Medicare Part B pays for biosimilars under the Physician Fee Schedule (PFS) based on the average sales price (ASP) of all biosimilar products within the same HCPCS code – grouping together all biosimilar products with the same reference product to calculate an ASP. This arrangement has meant that physicians are reimbursed the same amount for all biosimilars of the same reference product. The policy change is being welcomed warmly by many stakeholders including the Biosimilars Forum, professional bodies such as the American College of Rheumatology, and a number of patient organizations – who have all been actively campaigning for this amended policy to ensure a robust, competitive US biosimilars market. The coding change may also help reduce pharmacovigilance concerns among providers who are considering prescribing biosimilars.

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USA: New RAND Corporation forecast predicts savings from biosimilars of $54 billion in next 10 years

The widespread introduction of biosimilars could cut healthcare spending in the US by $54 billion over the next decade, according to a new analysis from the RAND Corporation. The savings estimate is about 20% higher than a similar analysis done by RAND researchers 3 years ago, representing both improved analysis methods and the rapid growth in spending on biologics overall. The report states a number of assumptions, which underpinned the prediction, and also acknowledges that the savings achieved will hinge on the evolving competitive landscape, on regulatory decisions, and on insurer efforts to promote biosimilar uptake through payment rates and other strategies. The authors further comment that it remains to be seen who will actually benefit from the savings.

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USA: FDA launches new biosimilars educational campaign for prescribers

The US Food and Drug Administration (FDA) has announced the launch of a new educational initiative on biosimilars “to help healthcare providers gain a better understanding of these important products and the approval process they undergo.” A major new section of the FDA’s website provides downloadable factsheets and infographics on biosimilars for prescribers, as well as materials for organizations to use in disseminating this information to interested parties. The available resources give basic definitions of key terminology, describe the rigorous standards any biosimilar must meet to gain approval (and how the FDA approval pathway works), and provide digestible information about the data and information the FDA reviews to determine biosimilarity. The new website also raises awareness about an important FDA reference source on biosimilars known as the Purple Book, and offers access to online presentations, courses, and webinars. The FDA plans to embark shortly on additional research with healthcare professionals to learn more about the types of information they need to effectively communicate about biosimilars with their patients.

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LATIN AMERICA: Conflict erupts in Columbia over plans for an abbreviated route to biosimilar approval

Colombia’s Health Ministry and the Columbian research and development-based pharmaceutical industry association, Afidro, are at loggerheads over proposed legislation that gives biosimilars a faster route to market. The legislation in question sets out a controversial “abbreviated comparability route,” which reduces the requirement for comparative data (except for immunogenicity testing) with the aim of expediting patient access to affordable biologic therapies. The legislation finally came into force in August 2017 after several setbacks, but may yet be stopped in its tracks. Some months previously, Afidro had filed a complaint with the Council of State (Colombia’s highest court, presiding over administrative issues) demanding that the decree be suspended because the super-abbreviated route to approval is “not safe and does not conform to international standards.” In September, the Council of State finally allowed Afidro’s application and officially notified the Health Ministry. In response, the Health Ministry has accused Afidro of self-serving commercial interests. It insists that because the active ingredients in the reference products are widely known, the abbreviated pathway – which still calls for immunogenicity testing and robust pharmacovigilance – is justified. The Ministry has asked the Council of State to consider ethical standards that, in line with the Declaration of Helsinki, require that experiments on humans “should not be repeated to demonstrate things that have already been demonstrated.” In a counter-statement, Afidro maintained that an approval pathway that allows an applicant to rely entirely on the data of a third party, without doing clinical comparative studies, is not acceptable.

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ASIA PACIFIC: Australian Medical Association criticizes the national government's approach to biosimilars

The Australian Medical Association (AMA) has raised concerns about the national government’s “heavy handed” new proposals for boosting biosimilar uptake in Australia. Firstly, as part of a software update to doctors’ prescribing systems, the government is planning to include an alert to prescribers stating that biosimilars are “preferred” for treatment-naïve patients. The AMA maintains that use of this alert across the board is misleading, because it is based only on cost-effectiveness and not on other potentially significant clinical considerations. Secondly, the government has proposed reducing the level of authorization required to prescribe a biosimilar, while maintaining the need for this authorization in the case of originators. Under the Australian system, some prescriptions covered under the nation’s Pharmaceutical Benefit Scheme (PBS) must be approved on a case-by-case basis, because they have been deemed too costly for widespread use. However, some medicines may be prescribed under a “streamlined” arrangement using a special authority code. The AMA has criticized the government’s proposed action of moving biosimilar etanercept to a streamlined approach, while keeping originator etanercept at the highest level of authorization, on the basis that it undermines prescribing freedom. It argues that the government’s biosimilar awareness program should be given time to work and that biosimilar uptake will proceed naturally as more products enter the market. The AMA also noted that biosimilar and reference etanercept are actually listed at the same price on the PBS and commented that: “unless a biosimilar product is listed on the PBS for a significantly lower price, there appears no justification for applying different restrictions to the same medicine on the basis of brand.”

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November 2017   +

GLOBAL: AbbVie and Amgen settlement sets dates for adalimumab biosimilar launch in EU and US

AbbVie and Amgen have announced a global resolution of their prolonged intellectual property-related litigation over Amgen’s adalimumab biosimilar, which is licensed in the European Union and United States as Amgevita and Amjevita®, respectively. Under the settlement, AbbVie – makers of the originator Humira® – will grant Amgen a non-exclusive license to adalimumab commencing on October 16, 2018 in the EU, but not until January 31, 2023 in the US. The agreement also requires Amgen to pay royalties to AbbVie for sales of the biosimilar. AbbVie alleged that Amgen infringed on 61 adalimumab patents, but they only included 10 in the lawsuit that was brought before the biosimilar was approved. They further report that the exact terms of the agreement are confidential, but all pending litigation has been dropped, with Amgen acknowledging the validity of the claims. A specialist lawyer commented that “this is a win for AbbVie but arguably also a win for Amgen and the public,” because the Amgen launch date is earlier than the expiry date of all of Humira’s® numerous patents and this settlement “brings certainty.”

From a US perspective, however, the deal has massive cost implications for the Centers for Medicare & Medicaid Services (CMS). If just one competing biosimilar was marketed from 2019 until 2023 (as in the EU) and the total CMS spend on Humira® was consequently reduced by 15%, a total of $1.48 billion would be saved. Furthermore, the EU is currently seeing multiple competitors vying for a share of Humira’s® market, meaning that more than five adalimumab biosimilars could be launched in Europe before the US sees even one.

The deal has also prompted speculation about the implications for other biosimilar manufacturers. Some stakeholders have pointed out the resemblance of the AbbVie–Amgen deal to what has happened with “authorized generics,” where the manufacturer of a branded product approaching patent expiration comes to an agreement with a generic drug maker to produce the first generic version and expedite its launch. This allows the branded company to earn licensing fees and royalties on the drug, and limits the erosion of its market share by several generic manufacturers. Two overriding concerns with the prospect of “authorized biosimilars” are that the additional royalty or licensing fee is likely to elevate the price of the biosimilar and that competing biosimilar manufacturers will have greater difficulty edging their way into the market in the face of the agreement.

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GLOBAL: Radiographic progression comparable in patients receiving etanercept biosimilar versus originator

A global Phase 3 study (n=596) comparing Samsung Bioepis’ etanercept biosimilar SB4 to the originator Enbrel® has found that SB4 had comparable efficacy – including radiographic progression – in patients with rheumatoid arthritis (RA). SB4 has been approved by regulatory authorities in the EU, Australia, Canada, and South Korea. As part of the study, radiographs of the hands and feet were evaluated by two independent readers for changes in the modified total Sharp score (mTSS). Radiographic progression from baseline to week 52 was comparable between the groups, with an average change in mTSS of 0.45 and 0.74 in the SB4 and Enbrel® groups, respectively (95% CI, –0.80 to 0.26). The study concluded that SB4 is not only comparable to Enbrel® in terms of clinical efficacy (as measured by the ACR20 score), safety, and immunogenicity, but also comparably reduces the rate of radiographic progression.

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USA: Pfizer takes legal action on what it considers “anti-competitive practices” by Johnson & Johnson

Pfizer has sued Johnson & Johnson (J&J) in a federal court in Pennsylvania, alleging anti-competitive discounts and other actions intended to prevent competition by its licensed infliximab biosimilar Inflectra® with J&J’s originator Remicade®. The complaint illustrates the hurdles to successfully bringing a US biosimilar to market and provides a new opportunity for courts to evaluate the antitrust implications of loyalty discounts and “bundling.” According to the complaint, J&J has used rebates to induce major insurers to use Remicade® exclusively for both existing and new patients. Pfizer also alleges that J&J has bundled exclusive or near-exclusive purchases of Remicade® with purchases of other popular J&J products. J&J’s response was that – rather than asking a court to protect it from having to compete – Pfizer should work harder to demonstrate the overall value it can offer with its product and win the trust of physicians and patients.

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USA: New report claims revising CMS biosimilars policy could save $11.4 billion over 10 years

The Association for Accessible Medicines (AAM) and its Biosimilars Council, have released an analysis revealing that if the Centers for Medicare & Medicaid Services (CMS) were to revise its current reimbursement policy for biosimilar medicines, the federal government could save $11.4 billion over the next 10 years. CMS currently groups all biosimilars of a reference biologic under a single billing code and payment rate. A variety of stakeholders have raised concerns that this policy stifles the creation of a robust biosimilars market but, so far, changes to the policy have not been made. This latest report claims that although the CMS’s current reimbursement policy could produce short-term savings, this will be at the expense of much larger, long-term savings for Medicare. On this basis, the CMS has again been urged to revisit their policy and provide each non-interchangeable biosimilar for a given reference biologic with a unique billing code and payment rate.

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USA: FDA offers draft guidance on statistical approaches to evaluating biosimilarity

The US Food and Drug Administration (FDA) has released another piece of the biosimilars puzzle for industry, offering new draft guidance on the type of information a Sponsor should obtain about the structural/physicochemical and functional attributes of the reference product, how that information is used in the development of an analytical similarity assessment plan, and the statistical approaches recommended for evaluating analytical similarity. As part of the guidance, the FDA recommends that a minimum of 10 reference product lots be sampled and the lots “should represent the variability” of the reference product. It also recommends that a minimum of 10 biosimilar lots should be included in the analytical similarity assessment. The analytical similarity assessment plan, which should be submitted as part of a biosimilar application, should provide multiple testing results, indicate the differences in age of the lots produced at testing, provide information on assay performance, and point out differences in attributes that are not considered clinically meaningful. The FDA also lays out three tiers with appropriate similarity acceptance criteria that should help support a demonstration of similarity, based on the particular risk ranking of each quality attribute. However, biosimilar developers were reminded that approval is always based on “totality of the evidence” and not on the basis of a “pass or fail” for each individual element of the submission.

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USA: Latest attempt to gain regulatory approval of a biosimilar of pegfilgrastim stalls

The latest of several attempts to achieve approval of a biosimilar competitor to Amgen’s Neulasta® (pegfilgrastim) – this time by partners Biocon and Mylan – was stalled when the US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) citing manufacturing concerns. The FDA has previously criticized the manufacturing plant where Biocon is producing biosimilars for the US market, as has the European Medicines Agency (EMA), leading Biocon and Mylan to withdraw their EU applications for both the pegfilgrastim biosimilar and their trastuzumab biosimilar candidate. Biocon said the CRL didn’t raise questions about the safety or biosimilarity of its drug, but relates to an update on facility requalification activities following recent plant modifications. It said it would work quickly with the FDA to resolve the issues and that it does not expect a delay in getting the biosimilar to market.

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EUROPE: NHS England sets targets for biosimilar use in new and existing patients

The National Health Service (NHS) governing body in England has published new recommendations stating that at least 90% of new patients and at least 80% of existing patients should be prescribed the “best value biological medicine within 3 months of launch of a biosimilar medicine.” The document states: “Shared decision-making between clinical prescribers and patients will be vital if the best value, clinically effective medicines are to be used. Regional Medicines Optimization Committees will coordinate support and ensure plans are in place for the systematic uptake of biosimilar medicines by the end of 2017.” The new publication states: “As the biosimilar market develops, increased competition between biological medicines has the potential to deliver savings of at least £200m to £300m per year by 2020/21. This will help the NHS to maximize the value for patients from the amount it spends on these medicines and enable much-needed headroom for funding innovative treatments and/or improvements in pathways of care.”

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EUROPE: New President of Medicines for Europe launches "Access to Medicines" campaign

Marc-Alexander Mahl, the newly-elected President of Medicines for Europe, today launched the “Access to Medicines: Better Care for More Patients” campaign, calling on health ministers to fully embrace generic, biosimilar, and value-added medicines to improve the sustainability of healthcare systems across Europe. Dr Mahl explained: “The increasing overall cost of healthcare will force policymakers across Europe to make difficult and unpopular choices about how best to allocate resources. Yet there is a very simple and obvious way to ensure access while managing healthcare budgets: to promote generic, biosimilar, and value-added medicines use by patients, medical professionals, and pharmacists.” The new campaign will provide “compelling data and proposals to help policymakers and stakeholders improve access to medicines.”

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EUROPE: Majority of EU oncologists open to prescribing biosimilar trastuzumab

As the first biosimilar version of Roche's HER2-positive breast cancer treatment Herceptin® nears EU approval, 80 oncologists across Europe were polled on the likelihood that they will prescribe it. The results showed that, if healthcare payers choose to utilize the biosimilar – which has been developed by Samsung Bioepis and will be marketed by Merck & Co. as Ontruzant® – they will face minimal resistance from prescribers; indeed, most oncologists appear open to the idea of using a biosimilar if it improves access to what has become a cornerstone therapy for a sizeable proportion of breast cancer patients.

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October 2017   +

GLOBAL: Multinational, multidisciplinary task force endorses biosimilar switches in rheumatic diseases

A multidisciplinary task force comprising 25 experts from ten countries (eight European countries, the USA, and Japan) has concluded that sufficient scientific evidence exists to support the switch from originators to biosimilars to treat rheumatic diseases. The task force included experts in rheumatology, dermatology, and gastroenterology, as well as pharmacologists, patients, and a regulator. Their goal was to develop an evidence-based statement on the use of biosimilars in rheumatic diseases by assessing the available literature. Analysis of 29 publications led to five overarching principles and eight consensus recommendations covering issues such as clinical trials, immunogenicity, extrapolation of indications, switching between originators and biosimilars, switching from one biosimilar to another, and cost implications. The group concluded that biosimilars are unlikely to clinically differ from originators but encouraged healthcare providers to gather pharmacovigilance data in registries about the outcome of switches. Their report, “Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases,” has appeared in Annals of the Rheumatic Diseases.

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USA: FDA approves Amgen’s biosimilar of bevacizumab – first US biosimilar for cancer

The US Food and Drug Administration (FDA) has approved Amgen and Allergan’s Mvasi (bevacizumab-awwb) as a biosimilar to Roche’s Avastin® (bevacizumab). Mvasi has been approved for five types of malignancy (all the eligible indications of the originator), including non-squamous non-small cell lung cancer (NSCLC), colorectal cancer, and cervical cancer in combination with chemotherapy. Mvasi is the first biosimilar of bevacizumab approved in a highly regulated market and the first FDA-approved biosimilar for the treatment of cancer.

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USA: FDA approves its second adalimumab biosimilar

The US Food and Drug Administration (FDA) has approved Boehringer Ingelheim’s Cyltezo (adalimumab-adbm), which is the second FDA-approved biosimilar of AbbVie’s originator Humira®. Amgen’s Amjevita® (adalimumab-atto) was the first, approved in September 2016. Cyltezo was approved for the full range of indications attributed to Humira®. However, Humira® will not likely see biosimilar competition in the US market for at least another couple of years because of ongoing patent litigation.

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USA: Consumer survey indicates 60% would accept a biosimilar on cost grounds

A survey of approximately 2000 US registered voters, conducted by leading pharmacy benefits manager CVS Health, has reported that 60% of respondents would accept a biosimilar substitute for a brand name biologic if they found out it would save them money. CVS Health commented: “With more Americans taking prescription medications than ever before, generic and biosimilar drugs can be an important strategy to help keep costs down without sacrificing health outcomes, especially for families managing chronic diseases or multiple health issues. Insights from consumer services like this can be a valuable source of information as we shape programs and services."

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USA: US gastroenterologists may thwart payer mandates to use biosimilars by opting for alternative originators

A survey of US gastroenterologists (n=103) has revealed that, if a pharmacy or managed care plan advises use of biosimilar infliximab (Inflectra®) over the originator, Remicade®, one-third of prescribers are more likely to choose a different TNF-inhibitor altogether – usually Humira® (adalimumab). However, only one in five gastroenterologists report having received such contact from a pharmacy or insurance provider. Indeed, the most reported barrier to increased use of Inflectra® is a lack of insurance mandates, though as additional TNF-inhibitor biosimilars become available, payer pressure to switch from branded biologics to their biosimilar counterparts will likely increase.

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USA: Another follow-on insulin product (Sanofi’s Admelog®) wins tentative FDA approval

Sanofi has won tentative US Food and Drug Administration (FDA) approval for Admelog®, a follow-on biologic to Lilly’s Humalog® (insulin lispro injection), a rapid-acting human insulin analog. In a situation, which parallels that of the FDA’s recent tentative approval of Merck and Samsung Bioepis’ insulin glargine product Lusduna Nexvue, approval is tentative because it is subject to the resolution of patent infringement lawsuits. Such litigation triggers a stay on final FDA approval for up to 30 months, unless a court rules in favor of the company winning the tentative approval. This scenario arises only because, in the US, follow-on versions of insulin products are not approved under the FDA’s biosimilar pathway 351(k), but instead under the pre-existing 505(b)(2) pathway. Biologic products approved via 505(b)(2) are therefore referred to as “follow-on biologics” instead of biosimilars.

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USA: Biosimilars may extend biologic treatment to 1.2 million more people by 2025, new study suggests

The Association for Accessible Medicines (AAM) and its Biosimilars Council has announced the results of a new patient access study, Biosimilars in the United States: Providing More Patients Greater Access to Lifesaving Medicines. According to the new analysis (which was conducted by Avalere Health*), 1.2 million US patients could gain access to biologics by 2025 as the result of biosimilar availability. The study also suggests that women, lower income, and elderly patients would particularly benefit from access to biosimilar medicines.

“One of the key challenges our healthcare system must overcome," said Bruce A. Leicher, Chair of the Biosimilars Council, “is the lack of understanding by stakeholders – including those who stand to benefit from increased access to biosimilars – of the role biosimilars can have in treatment.” The Biosimilars Council has also issued an update to its handbook, The New Frontier for Improved Access to Medicines: Biosimilars & Interchangeable Biologic Products, an educational resource for patients, policymakers, health professionals, and other stakeholders.

*Avalere’s modeling was based on the expected growth of the top seven originator biologics through 2025 and assumed a similar increase in access due to the introduction of biosimilars as has occurred in the European Union. Demographics of the current population eligible for biologic therapy was determined using the 2014 Medical Expenditure Panel Survey (MEPS).

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EUROPE: European Society for Medical Oncology (ESMO) delegates witness race to trastuzumab biosimilar

This year’s European Society for Medical Oncology (ESMO) Annual Congress in Madrid, Spain featured as many as 30 presentations on biosimilars, as well as an ESMO Special Session on biosimilars with speakers representing clinicians, nurses, patients, and the European Medicines Agency (EMA). Most notably, three companies – Amgen/Allergan, Pfizer, and Celltrion – all announced positive Phase 3 data for their biosimilar trastuzumab candidates at ESMO. Sponsor attempts to differentiate their biosimilars from competitors are starting to emerge as the competition for the lucrative Herceptin® market intensifies. Currently, Samsung Bioepis appears likely to be first to market in the EU, after Mylan and Biocon were asked to withdraw their application for approval of their trastuzumab biosimilar in order to fulfil procedural requirements linked to re-inspection of their manufacturing facility in Bengaluru, India.

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EUROPE: Samsung Bioepis wins EMA approval for its adalimumab biosimilar

Almost at the same time as the US Food and Drug Administration (FDA) announced approval of Boehringer Ingelheim’s adalimumab biosimilar, Cyltezo, the European Medicines Agency (EMA) has announced approval of Samsung Bioepis’ version, Imraldi®. Imraldi® has been approved in the EU for all ten of Humira’s® existing indications. It is the second adalimumab biosimilar to be approved in Europe after Amgen's Amgevita, which was approved in March. Samsung Bioepis and Amgen are not expected to start marketing their biosimilars in the EU until after October 2018, when the primary patent protection for Humira® expires. In the meantime, AbbVie continues to seek new patent-protected indications for Humira® and recently gained a license for chronic non-infectious anterior uveitis in pediatric patients, the first product approved for this indication.

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EUROPE: Detailed comparison of biosimilar policies in European countries is published

Medicines for Europe has published a detailed analysis of biosimilar medicines policies across 31 European countries, detailing the status of availability, pricing systems, tendering, reimbursement, and benefit sharing for physicians, pharmacists, and patients. The review illustrates that European governments have realized that biosimilar medicines need a tailor-made policy framework and have disentangled their pricing policies from those of generic medicines. Physician-led switching and patient education remain the key drivers for increased use of biosimilar medicines. Adrian van den Hoven, Director General of Medicines for Europe, commented: “This overview shows that policy-makers need dedicated policies to provide more sustainable access to biosimilar medicines. Benefit sharing with stakeholders has proven to be the most successful approach to improving patient access and we encourage governments to learn from the best practices around Europe.”

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EUROPE: European Association of Hospital Pharmacists (EAHP) publishes biosimilars position paper

The European Association of Hospital Pharmacists (EAHP) has published a position paper on biosimilar medicines outlining its views on the role of the hospital pharmacist as well as on naming of biosimilars, extrapolation of indications, interchangeability, switching, and substitution. The EAHP position closely follows the European Medicine Agency’s (EMA’s) perspective and expresses confidence in the EMA’s regulatory pathway for biosimilars. The paper further states that hospital pharmacists are stewards of appropriate selection, procurement, logistics, and use of medicines, as well as key players in pharmacovigilance, and consequently are ideally positioned to promote the appropriate utilization of biosimilar medicines.

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September 2017   +

GLOBAL: New global market intelligence report compares “biosimilar friendliness” of regional markets

A new global market intelligence report from Netscribes Inc., which predicts that the global biosimilars market is expected to be worth US $36 billion by 2022, also takes a closer look at the market “favorability” for biosimilars across developed, BRIC and MIST countries.* Some of the major findings include:

  • Approval of 16–20 new biosimilars is predicted between 2018 and 2021 in both the US and EU
  • With a cumulative share of nearly 85%, North America, Europe, and Japan are the major contributors to global biologic and biosimilar sales; Asia and Africa account for 13.2% and 1.2%, respectively
  • South Africa is one of the best-suited markets for biosimilars due to a favorable regulatory environment and high prescriber acceptance.

The report includes a global “favorability matrix,” which assesses how “biosimilar friendly” each market is in terms of factors such as current access to biologics, the regulatory environment, the payer model, prescriber acceptance, patient acceptance, and current biosimilars presence.

*BRIC = Brazil, Russia, India, and China; MIST = Mexico, Indonesia, South Korea, and Turkey

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GLOBAL: Experts propose global reference comparator for biosimilars to eliminate costly bridging studies

In a recent journal publication, US-based biosimilar experts, Christopher Webster and Gillian Woollett, have asserted that bridging studies conducted between local and foreign versions of the same reference product are redundant, costly, and not scientifically necessary for biosimilar development. According to the authors, the inability of biosimilar sponsors to rely upon a single globally representative version of the reference product leads to the “grossly inefficient” replication of the same data by each sponsor and the potentially unethical inclusion of participants in unnecessary clinical studies.

Webster and Woollett argue the case for adoption of a “global reference comparator,” whereby a single approved version of an innovator’s product is used as the basis for development of a biosimilar, if three criteria are met:

  • The selected reference biologic is approved in a jurisdiction that has formally adopted the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines on comparability.
  • The selected reference biologic and the locally licensed reference product share the same pharmaceutical form, route of administration, content of active pharmaceutical ingredient, and composition of excipients. If there are excipient differences, then data must show these differences do not have any clinical effects.
  • There is substantial evidence in the public domain that the selected reference biologic and the locally licensed product have been approved on the basis of essentially the same original data, including clinical safety and effectiveness data.
“We recognize that there are a few biologics for which the reference bridging criteria above will not be appropriate, and that regulators will wish to evaluate the suitability of this approach on a case-by-case basis. However, we believe the approach is applicable to the majority of biologics, and that the adoption of the ‘global reference’ approach will significantly improve the efficiency of biosimilar development.” the authors claim.

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USA: Launch of second infliximab biosimilar initiates first US biosimilar price competition

A second biosimilar of infliximab, Merck and Samsung Bioepis’ Renflexis (infliximab-abda) – which gained FDA approval in April of this year for all the licensed indications of the originator, Remicade® – has been launched in the US at a 35% wholesale discount to the current list price of Remicade®. While multiple biosimilar versions of the same originator are already available in the EU, this is the first time that two competing biosimilars have been marketed in the US. The first US infliximab biosimilar – Pfizer’s Inflectra® (infliximab-dyyb) – was launched in November 2016 at a discount of 15% to Remicade’s® list price. The discount offered by Renflexis is therefore considerably greater.

According to Bloomberg analysts, Merck and Samsung are “setting a precedent by more than doubling Pfizer's discount in the lucrative US market despite being only the second biosimilar to arrive there. That discount comes before large insurers and pharmacy benefit managers have started negotiating their own price breaks.” The analysts further comment that Pfizer's brief period of having the only US-approved biosimilar for a particular originator will likely be the norm in the future, as the FDA speeds up with its biosimilar approvals. They add: “Eventually there may not even be a short honeymoon period of modest discounts for new biosimilars before cutthroat competition starts. The big positive of all this, of course, is that lower prices mean many more patients will get access to these medicines. But the biosimilar pie may be smaller and split more ways than some drugmakers expected.”

Another major consequence of the launch of Renflexis is that, for the first time, Medicare's controversial biosimilars reimbursement policy has been triggered. Because both Renflexis and Inflectra® are infusible products that would be administered in a physician's office or outpatient center, their Medicare coverage falls under Part B. Under the existing policy, Medicare Part B will pay for biosimilars that reference the same innovator drug under one reimbursement code at a single blended payment rate (plus 6% of the average sales price of the reference drug). Biosimilar developers have strongly objected to this blended payment approach because they believe it would lead to a “race to the bottom” on pricing and present a disincentive for biosimilars that are first to market. With the launch of Renflexis,opponents such as the Biosimilars Forum now also argue that Merck's pricing strategy demonstrates that market forces will be effective in driving down the price of competing biosimilars and that Medicare does not need to intensify competition through payment policies. In the meantime, the Biosimilars Forum and other stakeholders are once more calling for separate reimbursement codes and payment rates for each biosimilar.

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USA: FDA panel unanimously backs biosimilars of bevacizumab and trastuzumab

The US Food and Drug Administration’s (FDA’s) Oncologic Drugs Advisory Committee (ODAC) has unanimously backed the approval of biosimilar versions of two of Roche's top selling cancer drugs, Avastin® (bevacizumab) and Herceptin® (trastuzumab). ODAC members voted 17–0 in favor of approving Amgen's bevacizumab biosimilar candidate, ABP 215, for six of Avastin's indications. The committee did not consider whether Amgen's data would support approval for Avastin’s two ovarian cancer indications, as these are covered by orphan drug exclusivity until 2021 and 2023. ODAC members also voted 16–0 in favor of approving Mylan's trastuzumab biosimilar candidate, MYL-14010, for all of Herceptin's® indications, including an indication for metastatic gastric cancer, which is protected by orphan drug exclusivity through October 20, 2017.

In both cases, ODAC and FDA reviewers agreed that there were no clinically meaningful differences between the reference products and the biosimilars, though some panel members expressed concerns about extrapolating data from studies in a single disease to multiple indications. But ODAC Chair Bruce Roth, a Professor of Medicine at the Washington University School of Medicine, reminded the panel that oncologists have to extrapolate data every day in the clinic. “I think the magnitude of extrapolation is no greater here than we experience on a daily basis in the clinic,” he said.

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USA: Merck and Samsung Bioepis’ insulin glargine product wins “tentative” FDA approval

Merck and Samsung Bioepis have won “tentative” US Food and Drug Administration (FDA) approval for Lusduna Nexvue, their version of Sanofi’s insulin glargine (Lantus®). The approval is tentative because Sanofi has sued Merck, contending that Lusduna infringes on unexpired Lantus® patents.

The FDA’s decision comes 6 months after Lusduna’s approval in Europe as a biosimilar to Lantus. In the US, Lusduna was not approved under the FDA’s biosimilar pathway (351(k)), but instead under the pre-existing 505(b)(2) pathway. Biologic products approved via 505(b)(2) are therefore referred to as “follow-on biologics” instead of biosimilars. Under the Hatch-Waxman Act, which governs the 505(b)(2) pathway, the filing of a lawsuit by Sanofi in September 2016 automatically blocks the FDA from issuing a final approval for Lusduna for up to 30 months, or if the District Court in Delaware rules in favor of Merck, whichever comes sooner. Once fully approved, Lusduna will be the second licensed insulin glargine follow-on biologic in the US, after Eli Lilly’s Basaglar®.

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EUROPE: New publication reviews supply-side and demand-side biosimilar policies across 10 EU countries

In an attempt to clarify the drivers for biosimilar uptake across Europe, a comprehensive literature review sponsored by Sandoz has been undertaken to identify supply-side and demand-side biosimilar policies across ten EU markets (Belgium, France, Germany, Greece, Hungary, Italy, Poland, Spain, Sweden, and the UK).

Key findings were as follows:

  • Supply-side policies for biosimilars commonly include price linkage, price re-evaluation and tendering
  • The use of internal or external reference pricing varies between countries and health technology assessment is conducted in only six out of the ten countries studied
  • With regard to demand-side policies, pharmaceutical prescription budgets (or quotas) exist in eight out of ten countries and monitoring of prescriptions (with potential financial incentives or penalties) are in place in seven countries
  • Switching is allowed, as long as it is prescriber-led; automatic substitution is not recommended, or is even forbidden by law, in most EU member states
  • Prescription conditions or guidelines that apply to biosimilars are established in nearly all surveyed countries.


The researchers conclude that significant heterogeneity in biosimilar policies exists between (and even within) the countries included in the study, which may partly explain variations in biosimilar uptake. Despite short-term savings, supply-side policies targeting price have been reported to limit biosimilar penetration in the long term, while demand-side policies are considered to positively impact uptake.

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EUROPE: UK survey highlights rheumatology patients’ understanding and attitudes towards biosimilars

A UK web-based study conducted among members of the National Rheumatoid Arthritis Society and the National Ankylosing Spondylitis Society (n=182) – who were receiving treatment with either etanercept or infliximab – has revealed a good overall level of patient knowledge and understanding about the use of biosimilars in rheumatology.

The study found that 66% of patients receiving originator biologics and 80% of those receiving biosimilars, understood what biosimilars were. Patients who were initiated on biosimilars had greater confidence in their effectiveness and the doctor’s decision to initiate them than those who were originally on originator biologics, whose doctor had proposed a switch to a biosimilar. The majority (82%) of participants on biosimilars thought that biosimilars help to save money for the UK’s National Health Service (NHS), while just over half (54%) of participants on the originator biologics thought the cost of treatment should not affect prescribing decisions. Those patients who expressed concerns felt that more clinical trials on switching to biosimilars, better communication and reassurance by healthcare professional teams, and further patient involvement in decision-making would increase their acceptance of biosimilars.

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EUROPE: Irish government launches public consultation on biosimilars

The Republic of Ireland’s Minister for Health, Simon Harris, has announced the official launch of a public consultation on biosimilar medicines. The consultation will inform the development of Ireland’s first National Biosimilar Medicines Policy, with the aim of increasing the use of biosimilar medicines across Ireland. Minister Harris commented: “It is vital that we ensure patients have access to a sustainable supply of safe and effective medicines. Despite the opportunities presented by biosimilars, uptake in Ireland remains low in comparison to many member states. An evidence-based National Biosimilar Medicines Policy will provide clarity and certainty to the health service, industry and patients on the use of biosimilars and will ensure that Government remains focused on its commitment to deliver greater value for our pharmaceutical spend.”

However, Medicines for Ireland, an industry group that represents generic and biosimilar manufacturers, says the “most significant obstacle currently to increased uptake of biosimilars is the State itself.” This, it says, is due to a biosimilars “blocker clause” in the Framework Agreement on the Supply and Pricing of Medicine, which the Minister and innovative pharmaceutical sector signed last year. The clause in question stipulates that originator biologic manufacturers must cut the price of their products by 30% when a biosimilar competitor enters the market. The biosimilar producers say this makes it uneconomic for them to compete. And if they are deterred from competing, the price of the drug will not come down at all. Sandra Gannon, joint chairperson of Medicines for Ireland, welcomed the consultation paper but said that “meaningful action must follow...if Irish patients are to have access to more affordable and equally effective biosimilar medicines”. The consultation paper is available online at with a closing date of September 22, 2017.

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CANADA: Canadian hematology and oncology experts develop guiding principles for biosimilar use

A panel of Canadian hematologists and oncologists have formulated a set of guiding principles on biosimilar development within their clinical field. Representing the CARE (Community Academic Research Education) Faculty – a national group of specialists that develops education initiatives directed at their peers, as well as at nurses, pharmacists, patients, government, and payers – the hematology and oncology panel aims to equip Canadian healthcare providers with overarching recommendations to help inform their treatment decisions.

As part of their guiding principles, the panel raises concerns and the need for caution in the following areas:

  • The fact that biosimilars are approved by Health Canada based on studies comparing single agent activity, whereas most biologics are clinically used in combination
  • The use of surrogate endpoints that are not tied to meaningful efficacy endpoints
  • Extrapolating data from one cancer site to another based on pre-authorized indications for the originator biologic
  • Switching a patient stabilized on an originator to a biosimilar in the absence of peer-reviewed evidence.


The panel makes the following recommendations:

  • The decision to switch from an originator to a biosimilar should always be prescriber-led
  • Traceability is always needed to determine which biologic was given to individual patients
  • Biosimilar development should take into consideration input from patient and disease advocacy groups to ensure that patient and disease-specific concerns are addressed early and fully
  • Public (not just patient) education about biosimilars should be considered at the provincial and/or national level
  • Biosimilar developers should be encouraged to create some additional value for patient care (e.g. pre-filled syringes, greater room temperature stability or longer shelf life), rather than simply focusing on creating a sufficiently similar product.


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August 2017   +

GLOBAL: Systematic literature review dismisses concerns about switching from originators to biosimilars

A new systematic literature review conducted by authors in Eastern Europe and the Netherlands has concluded that concerns about switching clinically stable patients from an originator to a biosimilar are “overhyped.” Fifty-eight papers (12 empirical papers, 5 systematic reviews, and 41 non-empirical papers) were included in the review, which found that “preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access.”

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USA: Supreme Court rules that biosimilars need not wait 180 days after FDA approval before launching

In an important and decisive victory for the US biosimilars industry, the US Supreme Court has overturned an earlier ruling by a Federal Appeals Court that had mandated the need for biosimilar makers to provide originator manufacturers with 180 days’ notice of their intention to launch after gaining US Food and Drug Administration (FDA) approval. In their unanimous verdict, the Supreme Court justices ruled that the notice period could begin prior to FDA approval. Sandoz and Amgen, the two parties involved in the case, had been battling since 2014 over conflicting interpretations of the Biologics Price Competition and Innovation Act (BPCIA), which established an expedited path for regulatory approval of biosimilars.

According to the Supreme Court’s ruling, Sandoz’s notice, given in 2014 while their application for approval of Zarxio® (a biosimilar of filgrastim) was pending with the FDA, satisfied the BPCIA’s requirement. “In sum, because Sandoz fully complied with [the BPCIA] when it first gave notice (before licensure) in July 2014, the Federal Circuit erred in issuing a federal injunction prohibiting Sandoz from marketing Zarxio® until 180 days after licensure,” Justice Clarence Thomas wrote. He added that the ruling was based on the wording of the BPCIA, which he said does not impose the timing requirements that the Federal Circuit did in granting its injunction. “Even if we were persuaded that Amgen had the better of the policy arguments, those arguments could not overcome the statute’s plain language, which is our ‘primary guide’ to Congress’ preferred policy,” Thomas wrote. The ruling was applauded not only by Sandoz but by many other biosimilar developers and advocates who view it as a significant milestone for the US biosimilars industry.

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USA: FDA issues complete response letters for pegfilgrastim and epoetin alfa biosimilar applications

The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Coherus BioSciences, rejecting its application for CHS-1701, a candidate biosimilar of pegfilgrastim (Amgen’s Neulasta®), which Coherus has referred to as the highest selling oncology biologic in the US. The FDA has not requested a clinical study of CHS-1701 in oncology patients (as anticipated by some), but its CRL asks Coherus to reanalyse a subset of samples with a revised immunogenicity assay and to provide additional manufacturing-related information. News of this setback comes just 5 months after Sandoz withdrew its pegfilgrastim product from European Medicines Agency (EMA) consideration after being issued a list of questions, and also having received its own CRL from the FDA. Coherus has said that it will work with the FDA to address the outstanding concerns but, in the coming months, all industry eyes are likely to be on Mylan and Biocon’s attempt at a pegfilgrastim biosimilar, MYL-1401H.

Meanwhile, the FDA has also issued a CRL to Pfizer, rejecting its biosimilar of Amgen’s epoetin alfa (Epogen®) for the second time. Just a month previously, an FDA advisory committee had strongly recommended Pfizer’s epoetin alfa biosimilar for approval by a vote of 14–1. The reason for the CRL – which came as a surprise to many – related purely to Pfizer’s proposal to manufacture the product at a facility in McPherson, Kansas, USA, which had been criticised by the FDA on previous occasions for falling short of quality standards.

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USA: Acceptance of biosimilars by US health insurers is undermined by reduced profits for providers

According to a new report from healthcare consultancy Avalere Health, biosimilars are steadily gaining acceptance by the US health insurance industry. A survey of 45 health plans shows 81% are covering at least one biosimilar product, in the interests of achieving cost savings without comprising efficacy or safety. Ironically, however, a new study announced by another healthcare consultancy, Navigant, has shown that use of biosimilar drugs leads to a reduction in savings for most providers. Although biosimilars have the potential to reduce treatment costs, the savings are not realized for most providers mainly due to the “buy-and-bill” reimbursement model for infused therapies. The Centers for Medicare & Medicaid Services (CMS) incentivizes the use of biosimilars through reimbursement, but private payers generally don't, the Navigant study said. Because the reimbursement under CMS is more favorable, biosimilars become more attractive as the percentage of Medicare patients increases – but the fact that over 50% of a provider’s business needs to come from Medicare to make a biosimilar an economical choice means the situation is unrealistic.

A recent viewpoint column published online in JAMA Oncology, lists other barriers to US cost savings from biosimilars, including: the modest discounts for biosimilars launched so far in the US; a 12-year period of market exclusivity for originator biologics; a patent resolution process under the Biologics Price Competition and Innovation Act (BPCIA) that has resulted in numerous lawsuits; and the lengthy delays in finalizing the FDA’s guidance on biosimilar interchangeability.

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EUROPE: Double EMA approvals for Sandoz biosimilars of rituximab and etanercept

The European Medicines Agency (EMA) has approved two new biosimilars from Sandoz: Rixathon®, a biosimilar of rituximab, and Erelzi®, a biosimilar of etanercept. Rixathon® – the second rituximab biosimilar approved by the EMA after Celltrion’s Truxima a few months previously – was approved for use in all licensed indications of the originator (Roche’s MabThera®), including non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis. Erelzi® – the second etanercept biosimilar approved by the EMA after Biogen’s Benepali® – was also approved for all licensed indications of its originator (Amgen’s Enbrel®) including rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis, psoriatic arthritis, and juvenile idiopathic arthritis.

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EUROPE: Researchers speculate if “nocebo” effect could account for patients’ reactions to biosimilar switch

A real-world study of patients in Sweden (n=2938) who were switched from originator etanercept (Enbrel®) to a biosimilar (Biogen’s Benepali®) has found that 11% switched back after a median of 55 days. However, Lara Lucchese, Senior Consultant at QuintilesIMS in London, UK, who was one of the study investigators, stated that the data must be interpreted with caution because the reasons for switching back were unknown, and might be explained by patient/physician beliefs and expectations, principally the “nocebo” effect. Following its approval in April 2016, the number of prescriptions for Benepali® increased steadily, accounting for 50% of the Swedish etanercept market in less than a year, even though the use of biosimilars is not compulsory in Sweden. The study investigators speculated that the speed of uptake may have left little time for appropriate patient communication and education. “If I switch a patient to a biosimilar drug, and tell them that I’m sorry but I have to provide the cheaper drug now because the GDP is so low in our country, then you have the so-called nocebo effect. You have already introduced a negative impact on the efficacy of the treatment.” they observed.

Biogen has been quick to reveal its own real-world data, which showed that – in 1548 patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who were switched from Enbrel® to Benepali® – disease activity at 3 months post-switch was comparable with that observed in the 3 months prior to the switch. In presentations at this year’s Annual European Congress of Rheumatology (EULAR), Biogen also shared data from the UK and the Netherlands highlighting patient acceptance of Benepali and adherence to treatment among those who were switched from reference etanercept according to a defined transition protocol.

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EUROPE: Mandatory biosimilar switching in Denmark does not cause increase in demand for healthcare support

Danish researchers have revealed that a government-mandated switch from originator infliximab (Remicade®) to the biosimilar CT-P13 (which was 64% cheaper) over a period of only 2 months, did not – as feared – lead to a heightened demand for healthcare support. There was concern at the time that patient and physician anxiety about biosimilars – and the rapidity of the switch period – would result in an increase in healthcare resource utilization, which could offset the cost savings. However, it turned out in the end that there was no significant escalation in use of healthcare resources.

Nonetheless, to address the doubts and unease expressed by patients who were interviewed about the switch, the Danish Rheumatism Association participated in a national program, the details of which were presented at this year’s Annual European Congress of Rheumatology (EULAR) in Madrid. Implemented throughout 2016, the program focused on monitoring the efficacy and safety of biologics and biosimilars at a batch level, as well as a national level, and the provision of more comprehensive, independent patient information. In addition, regional hospitals have invited a representative from the Danish Rheumatism Association to participate in a working group, which aims to include the patient perspective in future national recommendations on the use of biologics and biosimilars.

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ASIA PACIFIC: Australia’s PBAC issues public statement on its biosimilars policy

The independent Pharmaceutical Benefits Advisory Committee (PBAC) – which makes recommendations to the Australian Government on what medicines should be subsidised for consumers – has issued a public statement intended to offer reassurance about the safety of biosimilars in the wake of its controversial “A” flagging policy. This policy designates approved biosimilars as interchangeable with their originators and hence substitutable by pharmacists. In its statement, the PBAC said it was concerned about the possible spread of misinformation regarding biosimilar safety and the details of its policies. The statement included a link to information providing scientific justification for A flagging, and went on to say that switching to biosimilars is nonetheless not mandatory and that physicians may still choose to prescribe by brand name to avoid biosimilar substitution (or to tick a box on the prescription forbidding substitution). The PBAC also stressed that patients also continue to have the ultimate say regarding which product they receive.

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July 2017   +

GLOBAL: Positive trial results announced at ASCO for two more proposed trastuzumab biosimilars

Two candidate trastuzumab biosimilars (Samsung Bioepis’ SB3 and Celltrion’s CT-P6) have shown therapeutic equivalence to Herceptin® as adjuvant treatment for HER2-positive early breast cancer, according to the findings of two independent studies presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. SB3 was investigated in a double-blind randomized trial by a team from the University Hospital of Besançon, France, in 875 patients with HER2-positive early-stage or locally-advanced breast cancer. CT-P6 was investigated in a similar double-blind, randomized trial by a team from Imperial College Healthcare NHS Trust, London, UK, in 549 patients with HER2-positive early breast cancer. In both cases, efficacy (as measured by pathologic complete response [pCR]), safety, and immunogenicity were shown to be comparable to Herceptin. Licensed biosimilars of trastuzumab are eagerly anticipated worldwide. So far, only South Korea – and a number of less highly regulated countries – have approved a trastuzumab biosimilar, but several applications have been made to the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) by companies including Mylan and Amgen.

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GLOBAL: Cancer biosimilars take center stage in this month’s issue of "Future Oncology"

Five review articles focusing on biosimilars in oncology have been published this month in the journal Future Oncology. They address the impact biosimilars could have in the treatment of cancer; considerations for key stakeholders; the regulatory environment; the viewpoints of prescribers, payers, and patients; and how uptake can be encouraged. They also examine in detail the case of CT-P10, a biosimilar of rituximab, which was the first licensed biosimilar of a monoclonal antibody used in oncology.

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GLOBAL: Alternating between originator and biosimilar filgrastim over six cycles has positive outcome

A Phase 3, randomized, double-blind study in patients with breast cancer receiving neoadjuvant myelosuppressive chemotherapy (n=218) has shown that switching back and forth between originator filgrastim (Neupogen®) and biosimilar filgrastim (Zarxio) (5 µg/kg/day) over six cycles of treatment is no less effective or well tolerated than receiving either Neupogen or Zarxio throughout all six cycles. Presented at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, the German study, sponsored by Sandoz, not only adds to the wealth of evidence for the interchangeability of Neupogen and Zarxio, but is particularly noteworthy given the number of switches carried out between the two products.

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UNITED STATES: FDA panel backs Hospira's Epogen® biosimilar

The US Food and Drug Administration's (FDA’s) Oncologic Drugs Advisory Committee (ODAC) has voted 14 to 1 in support of approving Pfizer subsidiary Hospira's proposed biosimilar to Amgen's anemia drug Epogen® (epoetin alfa) for all four of its indications. Epogen is currently licensed to treat anemia in patients with chronic kidney disease, human immunodeficiency virus (HIV), and certain cancers; as well as to reduce the need for red blood cell transfusions as a result of loss of blood from surgery. While Hospira's epoetin alfa biosimilar has been approved in Europe since 2007, the FDA rejected the company's first attempt at US approval in October 2015, just after Pfizer completed its acquisition of Hospira. At the time, Pfizer said it had additional evidence it could use to support the application and signaled its intent to refile.

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June 2017   +

GLOBAL: WHO pilots scheme to make biosimilars available to poorer countries

In a bid to accelerate the availability of biosimilars in low- and middle-income countries, the World Health Organization (WHO) plans to launch a pilot project this year for “prequalifying” biosimilars, and is inviting manufacturers to submit applications for candidate biosimilars of two cancer treatments on the WHO Essential Medicines List: rituximab and trastuzumab. If the WHO finds that the biosimilars submitted for prequalification are sufficiently similar to originator products in terms of quality, safety, and efficacy, the medicines will be listed by WHO and become eligible for procurement by United Nations (UN) agencies. The WHO also plans to advocate for lower prices for all biologic drugs, including supporting countries’ efforts to develop price-setting strategies. Many low- and middle-income countries rely on WHO prequalification before buying medicines and a further benefit of the scheme could be to increase competition with consequent pressure on pricing. “Biosimilars could be game-changers for access to medicines for certain complex conditions.” said Suzanne Hill, WHO Director of Essential Medicines and Health Products.

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USA: FDA approves its fifth biosimilar

The United States Food and Drug Administration (FDA) has approved a second infliximab biosimilar, Samsung Bioepis’ Renflexis, which has been given the INN infliximab-abda. Renflexis is approved for all of the licensed indications of the originator Remicade®. While it is the fifth biosimilar to be approved in the US, so far only two (Novartis’ Zarxio and Pfizer’s Inflectra®) have been launched due to ongoing litigation proceedings. With the introduction of a second infliximab biosimilar, the US infliximab market may experience greater competitive pressure; so far sales of Remicade have not been substantially eroded by Inflectra, which was launched at a modest 15% discount.

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USA: JAMA publishes article reviewing obstacles to the adoption of biosimilars for chronic diseases

The Journal of the American Medical Association (JAMA) has published a comprehensive review article discussing barriers to the uptake of biosimilars in the US and how these might impact anticipated cost savings. The article considers regulatory issues, federal and state-level legislation, issues related to the healthcare system infrastructure, and originator manufacturer defence strategies. Among the topics are the regulatory hurdles around interchangeability, the reticence of some payers to use formulary utilization management strategies to promote the use of biosimilars, and the “rebate traps” implemented by some originator manufacturers to incentivize payers to remain loyal to their products.

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USA: BPC issues new white paper on US biosimilars policy

The Biologics Prescribers Collaborative (BPC), a project of the Alliance for Patient Access, has published a new white paper, “The State of Biosimilars Policy.” The paper is released in conjunction with a congressional briefing on Capitol Hill where experts will discuss the current biosimilars policy framework and its impact on prescribing, reimbursement, and usage. Addressed within the white paper are the topics of naming, interchangeability, indication extrapolation, labelling, Centers for Medicare and Medicaid Services (CMS) reimbursement, and the Biosimilar User Fee Act.

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USA: Apotex initiates citizen's petition with regard to pegfilgrastim biosimilar applications

Three weeks before the United States Food and Drug Administration (FDA) is to take action on Coherus BioSciences’ pegfilgrastim biosimilar application, Apotex has launched a citizen’s petition calling for an FDA mandate that biosimilar sponsors referencing Amgen’s Neulasta® should withdraw their applications if they have not conducted a comparative efficacy study or immunogenicity studies in at least one of Neulasta’s intended patient populations, not just in healthy volunteers. Underlying this petition is Apotex’s assertion that, for healthy subjects with normal absolute neutrophil counts (ANC) counts, comparative clinical studies administering pegfilgrastim alone would fail to demonstrate a lack of clinically meaningful differences between a proposed biosimilar and the originator.

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EUROPE: New EMA/EC guide on biosimilars highlights lack of safety concerns after 28 product approvals

The European Medicines Agency (EMA) and the European Commission (EC) have jointly published a new guide for healthcare professionals, which aims to provide up-to-date information on both the science and regulation underpinning biosimilars. The guide was developed in collaboration with EU scientific experts, in response to requests from healthcare professionals. Organizations from across the EU representing doctors, nurses, pharmacists, and patients have also shared insights, to ensure that the guide adequately addresses questions relevant to all key stakeholders. Within the guide, the EMA points out that 28 biosimilars have been approved in Europe over an 11 year period, with no safety concerns reported.

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EUROPE: New QuintilesIMS report confirms the beneficial effects of competition on cost of biologics across Europe

A new report prepared by QuintilesIMS at the request of the European Commission (EC), has found that – due to the introduction of competition – EU countries are achieving significant savings from biosimilars, even if their overall market share is low. Since the introduction of biosimilar granulocyte-colony stimulating factors (G-CSFs), the price per treatment day for the overall market (i.e. originator filgrastim and biosimilars) has fallen by an average of 27%. In the case of tumor necrosis factor (TNF) inhibitors, where biosimilars arrived more recently, there has been an overall average price drop of 10%. The report notes that considerable savings are apparent even if an originator biologic has only one biosimilar on the market but adds that, in the long term, it may be necessary to have multiple biosimilars in order to achieve the full effect of a competitive environment. This dynamic is proving very different to the situation with small molecule generics. The report further states that the experience so far with biosimilars across Europe illustrates the heterogeneity in rates of uptake between biosimilar products, therapy areas, and countries, observing that there is not just one formula that will work to achieve the full savings potential, but that learnings can be taken from all areas.

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EUROPE: New budget impact analysis forecasts potential effects of uptake of rituximab biosimilar across EU

A new publication has assessed the financial impact of the introduction of Celltrion’s rituximab biosimilar CT-P10 across 28 European countries for use in patients with cancer and rheumatoid arthritis. The budget impact analysis model assumed the cost of CT-P10 would be 70% of the cost of the originator and had the following conclusions based on three scenarios:

CT-P10 gains 30% market share
at 1 year

Projected savings of €90.04 million, allowing 7,531 additional patients (6.4% increase) to access rituximab treatment
CT-P10 gains 50% market share
at 1 year

Projected savings of €150.10 million, allowing 12,551 additional patients (10.7% increase) to access rituximab
CT-P10 gains 30%, 40%, and 50% market share in the 1st, 2nd and 3rd years, respectively
Over a 3-year time horizon, projected budget savings were approximately €570 million, equating to 47,695 additional patients able to access rituximab


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EUROPE: Sustained efficacy and safety shown after automatic substitution of infliximab biosimilar for Remicade® in large Danish registry study

One-year outcomes from the nationwide DANBIO Registry in Denmark have reported sustained efficacy and safety after 802 patients with inflammatory arthritis were switched within routine care from Remicade® to biosimilar infliximab (CT-P13, Remsima®) without a prescriber-led decision in each case. The authors state that, to their knowledge, this is the first study of large-scale, “non-medical” switching in routine care with prospective data collection. The 2016 NOR-SWITCH Study confirmed the appropriateness of switching from Remicade to biosimilar infliximab, but that was a formal, randomized clinical study in which patients were assigned to either remain on Remicade or switch to the biosimilar – an important distinction.

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May 2017   +

GLOBAL: Mylan’s deal with Roche clears path for first biosimilar version of trastuzumab

Mylan has announced it has reached a settlement over its patent dispute with Roche providing “a clear pathway” for the launch of its biosimilar version of Roche’s Herceptin® in highly regulated markets. Mylan submitted its data package based on the HERITAGE Study in metastatic HER2+ breast cancer to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) last year, and now expects its trastuzumab biosimilar to be the first to launch in the US and possibly elsewhere. Meanwhile, results from the APHINITY trial (Herceptin + Perjeta® for the treatment of HER2+ breast cancer in the adjuvant setting) indicate that Roche has positioned itself to defend the franchise's revenue by expanding further in combination therapy, and reducing direct competition with upcoming biosimilars.

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GLOBAL: New real-world data meta-analysis for biosimilar infliximab in IBD proves favorable

A new meta-analysis of results from 11 published real-world studies including 829 patients showed that CT-P13 (Remsima®/Inflectra®), a biosimilar of infliximab, has “excellent clinical efficacy and safety” in patients with inflammatory bowel disease (IBD) (Crohn’s disease or ulcerative colitis). The new data add to mounting evidence that supports the use of biosimilar infliximab in IBD. Academic organizations, such as ECCO (the European Crohn’s and Colitis Organisation), have now voiced their endorsement for use of the biosimilar both in treatment-naïve patients and in those already receiving the originator Remicade®.

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GLOBAL: Positive Phase 3 data announced for Sandoz’s adalimumab biosimilar

Sandoz has announced positive Phase 3 data for its adalimumab biosimilar GP2017, which met its primary endpoint in a head-to-head study versus Humira® in a 51-week study of patients with moderate-to-severe chronic plaque psoriasis. Sandoz is one of many biotech manufacturers hoping to market a biosimilar of adalimumab once the patent for Humira has expired and legal battles with AbbVie have been resolved.

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EUROPE: EMA approves Amgen’s Amgevita™ – the first EU adalimumab biosimilar

The European Medicines Agency (EMA) has granted marketing authorization for Amgen’s AmgevitaTM (biosimilar adalimumab) for all the indications of the originator Humira®, which are no longer patent-protected. These include moderate-to-severe rheumatoid arthritis, psoriatic arthritis, severe active ankylosing spondylitis (AS), severe axial spondyloarthritis without radiographic evidence of AS, moderate-to-severe chronic plaque psoriasis, moderate-to-severe hidradenitis suppurativa, non-infectious intermediate, posterior and panuveitis, moderate-to-severe Crohn's disease, and moderate-to-severe ulcerative colitis. Amgevita is also approved for the treatment of certain pediatric inflammatory diseases, including moderate-to-severe Crohn's disease (6 years of age and older), severe chronic plaque psoriasis (4 years of age and older), enthesitis-related arthritis (6 years of age and older) and polyarticular juvenile idiopathic arthritis (2 years of age and older). Amgevita received approval in the US last year (where the trade name is Amjevita® [adalimumab-atto]). Through a duplicate Marketing Authorization Application (MAA), Amgen has also received approval to use the brand name SolymbicTM, which is authorized for the same indications as Amgevita, except for polyarticular juvenile idiopathic arthritis. The EMA confirmed that Amgen was allowed to submit two MAAs due to potential existing patents in certain EU Member States regarding the polyarticular juvenile idiopathic arthritis indication. Apart from that, there is no difference between the two products.

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EUROPE: UK High Court rules against AbbVie’s attempts to defend Humira® from biosimilars

A UK High Court has ruled in favor of joint claimants Samsung Bioepis, Fujifilm Kyowa Kirin Biologics, and Biogen who are all developing biosimilars of adalimumab and who maintained that AbbVie – manufacturer of the originator Humira® – was attempting to block biosimilar competition inappropriately through enforcing extra patents related to dosing and specific indications. Judge Henry Carr of the England and Wales High Court invalidated those patents in a ruling on March 3, 2017, which is likely to influence decisions in other markets. While the ruling is an individual win for the claimant companies, it also underscores how AbbVie is losing ground in protecting its biggest seller.

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EUROPE: EULAR’s new rheumatoid arthritis guidelines recommend biosimilars over originators

As part of their update to their 2013 guidance on the management of rheumatoid arthritis, the European League Against Rheumatism (EULAR) has advised that biosimilar products should be used over more costly biologic DMARDs or targeted treatments.

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EUROPE: World’s first biosimilar of interferon beta-1a for multiple sclerosis approved in Russia

The Ministry of Health (MoH) of the Russian Federation has awarded local biotech company Biocad marketing authorization for its biosimilar of interferon beta-1a, based on Merck’s Rebif®, a leading treatment for relapsing-remitting multiple sclerosis (RRMS), which is included in all international recommendations and protocols. Biocad’s interferon beta-1a biosimilar is the only registered biosimilar of Rebif worldwide, and was reportedly developed in accordance with European Medicine Agency (EMA) guidelines. The new biosimilar will be available for Russian patients this year.

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EUROPE: EU industry groups urge caution when switching from one biosimilar to another

Three European trade groups representing originator manufacturers (The European Federation of Pharmaceutical Industries and Associations [EFPIA], the International Federation of Pharmaceutical Manufacturers & Associations [IFPMA], and European Biopharmaceutical Enterprises [EBE]) have sounded caution about the prospect of switching from one biosimilar to another. In a position paper (which also warns against switching between originators and biosimilars without full consideration of all the implications by the prescriber), they point out a lack of European Medicine Agency (EMA) regulatory requirements for individually approved biosimilars to the same originator product to be compared with each other and maintain: “Switching between biosimilars represents an unknown, and one that harbours considerable uncertainty.” But Dr Duncan Emerton, a UK-based biosimilars expert, explains that, although it is true that there is no regulatory requirement to compare two or more biosimilars with one another, the EMA uses the same standard whenever a new biosimilar is approved for the same originator biologic, so one would expect all approved biosimilars to deliver the same clinical outcome. He added that, because each new batch of any biologic will be subtly different from the next, switching a patient between biosimilars for the same originator carries no greater risk than switching a patient from the originator to one of the biosimilars.

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USA: American College of Rheumatology highlights access to biosimilars as a priority

The American College of Rheumatology (ACR) has announced its 2017 health policy priorities, providing detailed policy recommendations to improve access to care and treatments for the 54 million Americans living with arthritis and other rheumatologic diseases. Among its recommendations, the organization calls for adequate funding for US Food and Drug Administration (FDA) review of biosimilar applications to ensure the efficient introduction of additional safe and effective therapies that lower biologic drug costs.

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ASIA PACIFIC: Biocon/Mylan’s trastuzumab biosimilars given greater marketing freedom in India

The Delhi High Court has allowed Biocon and Mylan to market their trastuzumab biosimilar brands to treat three types of cancer. According to an earlier court ruling, the partner companies could sell their biosimilar in only one indication and could not use the data of Roche’s Herceptin® in package inserts for their brands CANMAbTM and HertrazTM. The court’s latest move, which allows the companies to use Roche’s product data in their package inserts, is expected to allow Biocon and Mylan to secure a greater share of the market.

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ASIA PACIFIC: Etanercept biosimilar Brenzys™ is “A” flagged by Australian PBAC

Merck Sharp & Dohme’s etanercept biosimilar Brenzys™ has been granted an “A” flag status by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). The “A” flag status means Brenzys and the originator etanercept, Enbrel®, are marked as equivalent in the Schedule of Pharmaceutical Benefits, for the purposes of substitution by the pharmacist at the point of dispensing for all the circumstances (restrictions) that apply to both brands. Although the substitution process is not automatic, prescribers who do not wish the brand to be substituted need to state this on the prescription, otherwise the pharmacist is free to dispense a biosimilar. If on the other hand, substitution has been permitted by the prescriber, the patient may choose which brand they wish to receive from the pharmacist. Australia is known for its bold stance on biosimilar interchangeability, which has caused some controversy both nationally and globally.

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April 2017   +

GLOBAL: New Crohn’s disease data announced for biosimilar infliximab

Pfizer’s Inflectra®, a biosimilar of infliximab – which received approval from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the management of inflammatory bowel disease (IBD) via extrapolation from data in rheumatoid arthritis – now has confirmatory data in Crohn’s disease. Presented at the 2017 European Crohn's and Colitis Organisation (ECCO) Congress in Barcelona, Spain, biosimilarity between Inflectra and the originator Remicade® was demonstrated in 214 patients with moderate-to-severe Crohn's disease treated with one or the other for 6 weeks. The study will eventually run for 54 weeks, and is also investigating the safety and efficacy of patients switched from Remicade to Inflectra, or vice versa. If those results are similarly positive, the study could support the FDA approval of Inflectra as an interchangeable biosimilar – possibly the first such FDA approval.

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EUROPE: Rituximab biosimilar approved in the EU

The European Medicines Agency (EMA) has approved Celltrion’s rituximab biosimilar Truxima® for all approved indications of the originator MabThera®/Rituxan®, including non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Truxima – which was recently approved in South Korea, its first market – is the first biosimilar approved for a cancer indication in Europe.

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EUROPE: UK managed switching program to biosimilar infliximab demonstrates cost benefits

UK research has shown how switching from originator to biosimilar infliximab can be achieved in practice with major cost savings. In a managed switching program, all 143 patients at the University of Southampton Hospital who were on Remicade®, were offered the opportunity to switch to the biosimilar, and all agreed to the switch. After the program began, drug acquisition costs fell by £40,000–£60,000 per month. Investment in the switching program, including a salary for an inflammatory bowel disease (IBD) specialist nurse and other support staff, amounted to only 12% of the eventual cost savings, which were shared equally between the hospital and local payers, and re-invested in improving the service and quality of care for the whole IBD patient population in the area.

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EUROPE: Ireland forced to face up to flawed biologic pricing policy

The Irish government has faced renewed criticism and concern about the drug pricing agreement it signed in 2016 requiring originator companies to cut the price of their products by 30% once a biosimilar enters the market. At the time, opponents of the scheme argued that this plan would deny biosimilars a competitive advantage and deter biosimilar manufacturers from investing in the Irish market. These predictions now appear to be confirmed: the etanercept biosimilar Benepali® (the only biosimilar drug introduced into the Irish market since the signing of the Framework Agreement on Supply and Pricing of Medicines in August 2016) sold just three packets by the end of the year, despite its success in other markets. In contrast, Benepali’s off-patent branded competitor, Enbrel®, still sold close to 10,000 packets in Ireland over the same period, despite still being 10% more expensive. Medicines for Europe has called on Ireland to adopt policies that increase uptake of biosimilars in the country. The lobbying effort comes in the run up to publication of a government consultation document on the legal actions Ireland needs to take to encourage greater use of biosimilars.

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USA: US generics and biosimilars association re-brands and launches new campaign

The US Generic Pharmaceutical Association has rebranded to become the Association for Accessible Medicines (AAM), covering both generics and biosimilars. Its accompanying campaign is entitled “Keeping Medicines Within Reach.” In contrast to the PhRMA’s new “Go Boldly” campaign launched in late January, which sidestepped pricing concerns and highlighted bold science and innovation, the AAM’s new campaign emphasizes the need for affordability of medicines. Along with their main advert, the AAM also include four videos highlighting patients’ and their families’ personal stories, which will be featured in broadcast and digital advertizing as well as on social media.

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March 2017   +

Amgen’s two adalimumab biosimilar candidates recommended for EMA approval

Amgen’s AmgevitaTM and SolymbicTM have become the first biosimilars of AbbVie’s Humira® (adalimumab) recommended for approval in the European Union (EU) by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The products are identical molecules (ABP 501) but Amgen has pursued a “two brand” strategy to accommodate marketing considerations in different countries. Amgevita will be indicated in the EU as a treatment for a range of arthritic and psoriatic conditions – including rheumatoid arthritis and plaque psoriasis – in addition to Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. Solymbic is indicated for a slightly narrower range of these conditions, as well as enthesitis-related arthritis, which Amgevita does not share. The product was approved in the United States (US) in September 2016, where it is known as Amjevita® (adalimumab-atto), although patent disputes with AbbVie could delay its US launch until 2018 or 2019. Humira’s main EU patents are set to expire in 2018.

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AbbVie’s patent defence of Humira® goes on trial in UK court

A lawsuit brought jointly by Samsung Bioepis, its partner Biogen and Japanese drugmaker Fujifilm Kyowa Kirin Biologics (FKB) against AbbVie and its patent defence strategy for its top-selling biologic Humira® has commenced in the UK High Court of Justice in London. The claimants have asked the court to invalidate AbbVie’s “overlapping” secondary patents for Humira so they can launch biosimilar versions once the drug’s main patent expires in Europe in 2018. They claim that AbbVie has been filing new patents for Humira within specific indications and specific clinical scenarios with the sole purpose of fending off legitimate biosimilar competition. A win for the claimants would pave the way for them and others to commercialize adalimumab biosimilars in the UK and other European markets, since the UK ruling is likely to influence future patent jurisdictions in neighbouring countries.

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Positive Phase 3 data announced for two more adalimumab biosimilar candidates

In the wake of US and EU regulatory success for Amgen’s adalimumab biosimilar, positive Phase 3 data for adalimumab biosimilar candidates has been reported by both Pfizer and Coherus BioSciences. Pfizer’s product PF-06410293 was compared with Humira® in patients with moderate-to-severe rheumatoid arthritis, who were also taking methotrexate. Coherus’s adalimumab biosimilar candidate CHS-1420 was compared with Humira in patients with active, moderate-to-severe chronic plaque psoriasis. Several other companies, including a joint venture between Samsung Biologics and Biogen, Boehringer Ingelheim, Momenta Pharmaceuticals, and Sandoz are also developing adalimumab biosimilars.

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US Supreme Court to review biosimilar “patent dance”

The US Supreme Court has announced that it will review a controversial case between Sandoz and Amgen relating to whether biosimilar companies should have to wait 6 months after US Food and Drug Administration (FDA) approval before launching their products. The decision will impact not only the case in question (which stemmed from the commercialization of the first FDA-approved biosimilar ZarxioTM) but on the correct interpretation of the Biologics Price Competition and Innovation Act of 2009 (BPCIA) and the US biosimilar industry as a whole. The decision by the Supreme Court to take up the issue has caught some by surprise, particularly as so few biosimilars have come to market in the US and because, in December 2016, the Supreme Court declined to hear a similar dispute between Amgen and Apotex over what's known as the “patent dance,” a series of steps for the resolution of potential patent claims by an originator product manufacturer and a biosimilar applicant.

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Legal battle will delay US launch of Sandoz’s etanercept biosimilar Erelzi™ until 2018

Sandoz’s etanercept biosimilar ErelziTM, which was approved by the US Food and Drug Administration (FDA) in mid-2016, looks unlikely to reach the US market before mid-2018, due to ongoing legal battles with Amgen, the maker of the originator biologic Enbrel®. A delay between the licensing and launch of Erelzi had been anticipated due to Amgen’s patent lawsuit, but a delay of as much as 2 years had not been foreseen.

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Janssen launches lawsuit to halt US sales of infliximab biosimilar and recoup “lost” profits

Janssen Biotech has asserted that Celltrion Healthcare has infringed a patent related to their originator product Remicade® (infliximab) in the manufacture of Celltrion’s biosimilar InflectraTM. A Massachusetts Federal Court heard that, according to Janssen, Celltrion has been using a patent-protected cell growth powder to produce batches of Inflectra, and should reimburse Janssen for all lost profits since the US launch of the biosimilar competitor late in 2016 and cease to market the biosimilar nationwide. Celltrion disagrees that the patent was infringed.

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US FDA issues long-awaited biosimilar interchangeability guidance

The US Food and Drug Administration (FDA) has released, for public consultation, its long-awaited draft guidance on the demonstration of biosimilar interchangeability. For both manufacturers and healthcare systems, interchangeability is seen as a major benefit since – where individual State legislation permits – biosimilars deemed interchangeable may be substituted for the originator by pharmacists without consulting the prescribing physician. The following key points were made in the FDA’s guidance:

  • Requirements for demonstrating interchangeability will vary depending on the product so biosimilar sponsors should consult with the FDA early on to discuss their plans.
  • When determining the type and amount of data needed, sponsors should consider an array of factors, including the product’s structural complexity, degree of analytical similarity to the originator and product-specific immunogenicity risk.
  • One or more switching studies should be carried out to demonstrate that patients can alternate between the originator and the biosimilar two or more times without diminished efficacy or safety.
  • Sponsors may use extrapolated data to support interchangeability for multiple indications if there is adequate scientific justification.
  • Sponsors conducting switching studies are strongly recommended to use a US-licensed originator product.
  • Sponsors should carefully consider their product presentation, including the delivery device and container closure system, because differences in presentation compared with that of the originator may affect the FDA's determination of interchangeability.

In general, stakeholders have reacted favorably to the guidance, which is seen as “workable” and in line with expectations.

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US FDA finalizes naming policy for biosimilars and originator biologics

In a departure from the approaches taken by the European Medicines Agency (EMA) and the World Health Organization (WHO), the US Food and Drug Administration (FDA) has finalized its guidance on how biosimilars and originator biologics should be named. It has been decided that product names should include a four-letter, FDA-designated meaningless suffix, attached to the nonproprietary name. It had previously been proposed that the suffixes should have a meaning, which assisted in identifying the manufacturer. For example, the first biosimilar approved by the FDA was Sandoz’s ZarxioTM, originally named filgrastim-sndz (“sndz” signifying Sandoz). However, this will now be changed to “filgrastim-bflm.” The random suffixes will not just be for biosimilars, but also for originator biologics. In line with this, the non-proprietary name of Amgen's Neupogen® (filgrastim) will be changed to “filgrastim-jcwp.” The FDA explained that nonproprietary names with distinguishing suffixes will help identify specific products in spontaneous adverse event reporting and to reinforce accurate product identification in billing and claims records used for active pharmacovigilance. The distinguishing suffixes should also help to minimize inadvertent substitution particularly for biosimilars that have not been deemed interchangeable with their originators.

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Medicare to cover infliximab biosimilar in US

Pfizer has announced that Medicare has released reimbursement information for its biosimilar InflectraTM (infliximab-dyyb). This indicates that Medicare intends to cover the product for qualified patients, although reimbursement may be declined under certain circumstances. Pfizer has also established a comprehensive reimbursement service and patient support program offering coding and reimbursement support for providers; co-pay assistance to eligible patients who have commercial insurance that covers Inflectra; and financial assistance for eligible uninsured and underinsured patients. Inflectra was approved by the US Food and Drug Administration (FDA) in April 2016 and launched in November of that year. It is priced at a 15% discount to the current wholesale acquisition cost for the originator (Remicade®), but this does not include discounts to providers, payers, and other groups involved in purchasing.

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US withdrawal from TPP releases member nations from set biologic exclusivity period

President Donald Trump’s withdrawal from the Trade Pacific Partnership (TPP) has imminent implications for biosimilars within the original member nations (Australia, Brunei, Canada, Chile, Japan, Malaysia, Mexico, New Zealand, Peru, Singapore, and Vietnam). The draft agreement endorsed by the Obama administration would have set a 5–8 year exclusivity period for originator biologics among the member nations (although these countries would have had to pass their own regulations to ensure enforcement of the global trade deal). With the scrapping of the deal, the member nations appear once again free to decide their own exclusivity periods for biologics. Meanwhile, despite the repeal of the Affordable Care Act by the Trump administration, biosimilars do not seem under threat in the US within the Trump era. President Trump has publicly voiced his concerns about the soaring costs of drugs in the US and biosimilars are seen as a useful way to curb this.

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ESMO endorses oncology biosimilars in new position paper

In a new position paper published by the European Society for Medical Oncology (ESMO), official endorsement has been given to the widespread use of oncology biosimilars as a means of improving patient access to important biologic treatments. “Biosimilars are must-have weaponry in financially sustaining healthcare systems on a global scale, as well as significantly improving outcomes for an increasing number of patients throughout Europe and the rest of the world.” ESMO President, Professor Fortunato Ciardiello, said in a statement. ESMO added that price discounts for biosimilars of 20–40% could be reached in Europe, with potential savings for healthcare systems of 50–100 billion euros ($53–107 billion) by 2020.

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European Commission publishes patient Q&A on biosimilars

The European Commission has published an authoritative new Q&A on biosimilar medicines intended to enhance understanding and trust in biosimilars among patients across Europe. Available in seven EU languages, the resource aims to provide unbiased, reliable, scientifically accurate, and easy to understand information. It was drafted with input from the European Medicines Agency (EMA), European Patients Forum (EPF), European Federation of Crohn's & Ulcerative Colitis Associations (EFCCA), the Standing Committee of European Doctors, the European Federation of Pharmaceutical Industries and Associations (EFPIA), European Association for Bio-industries (EuropaBio), and Medicines for Europe. In addition, for the third year in a row, the European Commission will organize a multi-stakeholder workshop on biosimilars to be held on May 5, 2017.

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EMA approves a second biosimilar of insulin glargine

The European Medicines Agency (EMA) has approved a new biosimilar of insulin glargine developed by US-based Merck Sharp & Dohme (MSD) with partial funding from Samsung Bioepis. MSD’s Lusduna – a biosimilar of Sanofi’s Lantus® – is the second insulin glargine biosimilar to be approved by the EMA after Eli Lilly’s Basaglar®.

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Novartis withdraws pegfilgrastim biosimilar candidate from EMA review

Novartis has decided to withdraw its European Medicines Agency (EMA) application for approval of ZioxtenzoTM, a pegfilgrastim biosimilar candidate based on Amgen’s Neulasta®. Initial review of the data package by the EMA’s Committee for Medicinal Products for Human Use (CHMP) had generated a list of questions. One of these concerns was that the study results had not demonstrated that blood levels of pegfilgrastim were the same after taking Zioxtenzo as after taking Neulasta. In its letter notifying the EMA of the withdrawal of the application, Novartis stated that it “would not be able to provide the additional data required by the CHMP within the timeframe allowed.” The decision comes about 6 months after Novartis received a ”complete response letter” from the US Food and Drug Administration (FDA) explaining why its application for US approval of the biosimilar could not be taken further without addressing outstanding questions.

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January 2017   +

Triple switch study confirms equivalence of etanercept biosimilar to Enbrel®

An innovative 52-week study in 531 patients with psoriasis has confirmed that three successive switches between branded etanercept (Enbrel®) and a biosimilar version showed no clinically meaningful differences between the two treatments. Published in the British Journal of Dermatology, the Sandoz-sponsored EGALITY study was carried out in 74 centers across Europe and South Africa. The study findings add to accumulating global evidence supporting switching between originators and approved biosimilars. Sandoz’s biosimilar of etanercept was approved by the US Food and Drug Administration (FDA) in August 2016 for all licensed indications of the originator, including rheumatoid arthritis, plaque psoriasis, and psoriatic arthritis.
It is currently under regulatory review by the European Medicines Agency (EMA) after the submission was accepted in the second half of 2015.

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EMA to pilot tailored advice on step-by-step development of new biosimilars

The European Medicines Agency (EMA) will launch a pilot project in February 2017 to test the added value and feasibility of tailored scientific advice for the development path of biosimilar medicines. Through this new initiative, the EMA aims to provide developers of biosimilars with advice on the studies/tests they should be conducting, based on the quality of the analytical and functional data they already have and how robust these data are. This is expected to better support the stepwise development of biosimilars, which is recommended in European Union (EU) guidelines. The EMA has also announced that:

  • Development of biosimilar heparins no longer requires a comparative clinical trial
    A new product-specific guideline for biosimilar heparin development is available here

  • A new educational resource on biosimilars is available for patients
    The EMA has published a new consumer-friendly Q&A resource entitled “Biosimilar medicines explained,” available here

  • A total of 17 biosimilars are under review by the EMA
    Amgen’s adalimumab biosimilar (a competitor to AbbVie’s Humira®), and three would-be competitors to Amgen’s own Neulasta® (pegfilgrastim), are among 17 biosimilar products currently under review by the EMA.

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US FDA finalises pharmacology guidance and advises biosimilar developers on best practice

Just before the end of 2016, the US Food and Drug Administration (FDA) announced it had finalized its draft 2014 guidance on the clinical pharmacology data required to support a proposed biosimilar application. Changes from the initial version were described as clarifications rather than substantive amends, but are important because clinical pharmacology studies are part of a stepwise approach for demonstrating biosimilarity and inform the design of subsequent clinical trials. In addition, in the run-up to the second Biosimilar User Fee Act (BsUFA II), which will indicate how the US biosimilars program needs to adapt over the next 5 years, top FDA officials have issued overarching advice to biosimilar developers:


  • Don’t do unnecessary studies: The FDA reminded industry that one of the key advantages of biosimilars is that they are approved via an abbreviated pathway. It has been noticed that biosimilar developers sometimes lose sight of the abbreviated nature of the 351(k) approval pathway and end up doing more work than necessary.

  • Aim for more advanced and more sensitive analytics: Because of the greater emphasis on analytical data for biosimilars, the FDA advised sponsors to look to develop new and innovative approaches to studying their products, with an emphasis on increasing the sensitivity of methods to detect potential differences between originators and biosimilar candidates.

  • Engage with regulators early on: The FDA encouraged developers to leverage the resources offered by the FDA, such as formal meetings with the agency from an early stage. It also explained how it is seeking alignment with other major regulators. Most notably, the biosimilars “cluster,” which comprises the FDA, the European Medicines Agency (EMA), Health Canada, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), and meets three times a year to share information and discuss development challenges. The cluster is not currently aiming for full regulatory harmonization, but instead scientific alignment. However, for now, developers are advised to approach each regulatory agency separately to ensure their individual needs are met for the market in question.

  • Adopt cutting-edge manufacturing methods: The FDA urged biosimilar developers to adopt modern manufacturing methods to produce these critical medicines as efficiently and economically as possible. While innovator manufacturers have so far taken the lead with advanced bioprocessing, the imperative is there for biosimilars to start to drive innovation in manufacturing, aligned with their goal of cost containment.


Sanford C. Bernstein financial analyst, Ronny Gal, speculated that, in the end, biosimilars may emerge as safer and more effective therapies than innovator products due to the utilization of more advanced analytics and more efficient production systems.

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JAMA Editors endorse trastuzumab biosimilar in light of Phase 3 data publication

The Journal of the American Medical Association (JAMA) has given prominence to the findings of the HERITAGE study reporting that Mylan & Biocon’s candidate trastuzumab biosimilar is clinically equivalent to the originator Herceptin®, for the treatment of HER2-positive metastatic breast cancer in combination with a taxane. Led by a team from the University of California-San Francisco, the study was conducted in several countries, including India, Thailand, Russia, and the Philippines. Mylan & Biocon submitted a marketing application to the EMA for their biosimilar in August 2016.

JAMA’s Editor-in-Chief Howard Bauchner, MD, observes (in an accompanying editorial entitled “Scientific evidence and financial obligations to ensure access to biosimilars for cancer treatment”) that the study “may influence care for patients with breast cancer around the world” especially where Herceptin is not widely available due to cost. In a second editorial, Harold J. Burstein, MD, Associate Professor of Medicine at Harvard Medical School and Deborah Schrag, MD, Associate Editor of JAMA write: “In answer to the proverbial question ‘Would you use the trastuzumab biosimilar for your mother if she had HER2-positive breast cancer?’, the answer should be ‘Yes’.”

This month, Pfizer announced that their investigational biosimilar drug, PF-05280014, also demonstrated equivalence to Herceptin, taken in combination with paclitaxel, in treatment-naïve patients with HER2-positive metastatic breast cancer.

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Major European study on real-world experience with oncology biosimilars welcomed in US

The US Oncology Network (a major network of integrated, community-based oncology practices) has called attention to a landmark series of articles entitled “Safety and efficacy of biosimilars in oncology” published this month by The Lancet Oncology. The study extensively reviews the real-world performance of oncology biosimilars such as filgrastim and epoetin since their introduction in Europe and confirms their highly similar safety and efficacy versus originators. The authors also predict future biosimilars will receive regulatory approvals with less extensive clinical testing, since analytics testing has greatly progressed over the past decade. One of the authors, Dr Robert Rifkin, Medical Oncologist at Rocky Mountain Cancer Centers in Denver, CO, USA, stated that the study provides America with much-needed information and added, “Key to success in the US will be a streamlined approach to how we develop, regulate, manage, and promote acceptance of these drugs to physicians and patients.”

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South Korea becomes first highly regulated market to approve a biosimilar of rituximab

South Korea has become the world’s first highly regulated market to approve a biosimilar of rituximab. Celltrion’s Truxima™ – based on Roche’s originator biologic Rituxan® – has received marketing approval in South Korea for the treatment of patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis. Global pharmaceutical companies including Amgen, Pfizer, and Boehringer Ingelheim have all been interested in developing a biosimilar version of rituximab, but it looks like Celltrion’s product may be first to gain approval beyond South Korea as it has now also been recommended for approval in Europe by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).

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EMA poised to approve first biosimilars of teriparatide

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has given a positive recommendation to approve the first biosimilars of teriparatide, a parathyroid hormone treatment for osteoporosis. The two teriparatide biosimilars, Movymia™ and Terrosa, are produced by German generics giant Stada Arzneimittel (Stada) and Hungary-based Gedeon Richter (Richter), respectively. The drugs are biosimilars of Eli Lilly’s osteoporosis treatment Forteo®/Forsteo® (teriparatide).

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Pfizer’s proposed trastuzumab biosimilar demonstrates equivalence to Herceptin®

Pfizer has announced that its Phase 3 study comparing PF-05280014, a proposed trastuzumab biosimilar, head-to-head with Herceptin®, has met its primary endpoint. The REFLECTIONS trial demonstrated equivalence in the primary endpoint of objective response rate (ORR) of PF-05280014 versus Herceptin, taken in combination with paclitaxel, in first line patients with HER2-positive metastatic breast cancer (n=226).

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Sandoz’s proposed rituximab biosimilar demonstrates equivalence to MabThera®

Sandoz has announced interim data from the ASSIST-FL trial comparing its candidate rituximab biosimilar GP2013 with the originator MabThera® in 629 patients with previously untreated follicular lymphoma. Consistent with clinical practice, patients in both arms also received cyclophosphamide, vincristine, and prednisone (CVP). The study – which is due to complete in 2018 – showed GP2013 met its primary endpoint of overall response rate (ORR). Results were presented at the 58th Annual Meeting of the American Society of Hematology (ASH).

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Momenta’s proposed adalimumab biosimilar proves equivalent to Humira® in psoriasis

US biotech Momenta Pharmaceuticals has reported that its candidate adalimumab biosimilar M923 has proved equivalent to Humira in a late-stage psoriasis study. In Momenta's trial, adult patients with moderate-to-severe chronic plaque psoriasis received up to 48 weeks of treatment of M923, Humira, or Humira alternating with M923. The percentage of patients achieving at least a 75% reduction on an index of psoriasis severity was equivalent between M923 and Humira, meeting the main goal of the study.

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Pfizer’s infliximab biosimilar and Eli Lilly/Boehringer Ingelheim’s follow-on insulin glargine launch in US

November 28, 2016 saw the launch of Inflectra® (infliximab-dyyb), Pfizer and Celltrion’s biosimilar of Janssen’s Remicade®. Inflectra received US Food and Drug Administration (FDA) approval in April 2016 and is being marketed at a 15% discount versus the wholesale cost of the originator. Pricing for the drug does not take into account discounts to health insurers, distributors, or other purchasing organizations, the company said. Uptake of Inflectra is expected to be boosted by the results of the Norwegian government’s NOR-SWITCH study, which showed that switching from originator to biosimilar infliximab did not result in any significant change in safety or efficacy.

In addition, Eli Lilly and Boehringer Ingelheim have announced the US launch of their insulin glargine product Basaglar® – a follow-on biologic for Sanofi’s Lantus®. Although Basaglar is approved as a biosimilar for Lantus in Europe, it is not technically considered a biosimilar in the US since it was approved via the 505(b)(2) regulatory pathway for follow-on drugs instead of the 351(k) pathway for biosimilars. Basaglar is 15% less expensive than Lantus, and the competitive pricing has already encouraged pharmacy benefit manager CVS Health to include Basaglar, rather than Lantus, on its 2017 formulary.

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Solicitor General advises Supreme Court to review 180-day biosimilar launch delay ruling

The US Solicitor General has recommended that the US Supreme Court review a heated dispute over a law that mandates biosimilar developers must give originator manufacturers 6 months’ notice following US Food and Drug Administration (FDA) approval before they are permitted to launch their product commercially. The case in question concerns Sandoz versus Amgen, and relates to the launch of the first FDA-approved biosimilar Zarxio™ (filgrastim-sndz). While this plays out, the Supreme Court has declined to hear a closely related appeal – Apotex versus Amgen – concerning the launch of a biosimilar of pegfilgrastim. All eyes are now on the Sandoz case and whether the Supreme Court will comply with the recommendation of the Solicitor General to review it.

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QuintilesIMS issues new prediction on US savings from biosimilars

A new forecast report from QuintilesIMS predicts savings of $27 to $58 billion from the use of biosimilars in the US over the next 5 years. The report also projects a slowdown in price increases for US branded drugs, possibly as a result of rising political pressure, although drug spending overall is expected to grow at an annual rate of 6–9%.

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New Biosimilars Forum survey identifies knowledge gaps among US prescribers

The results of a new survey of over 1,200 US clinicians published in the journal Advances in Therapy have shown that, although over 75% have heard about biosimilars, there are notable gaps in their knowledge about biosimilar concepts. Designed by the "Biosimilars Forum", a non-profit association of major US biosimilar developers, the survey highlighted five major gaps:

  1. Defining biosimilarity
  2. Understanding the approval process and the US Food and Drug Administration’s (FDA's) use of totality of evidence to evaluate biosimilars
  3. Appreciation that the safety profile of a biosimilar is expected to be the same as that of the originator biologic
  4. Understanding how decisions are made by the FDA for extrapolation of indications
  5. Defining interchangeability and the related rules regarding pharmacy-level substitution


“With four biosimilars approved by the FDA and more than 60 in development, the survey highlights the need for greater biosimilars education for physicians and healthcare professionals,” the lead author, Dr Hillel Cohen of Sandoz Inc., said.

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ECCO endorses switching to biosimilar infliximab in inflammatory bowel disease

The European Crohn’s and Colitis Organisation (ECCO) has issued a new statement on the use of biosimilars for inflammatory bowel disease (IBD), which supports switching from Remicade® to biosimilar infliximab. The statement confirms that:

  • Switching from the originator to a biosimilar in patients with IBD is acceptable following appropriate discussion between healthcare providers and patients.

  • When a biosimilar product is registered in the European Union (EU), it is considered as efficacious as the reference product when used in accordance with the Summary of Product Characteristics.

  • Data for the usage of biosimilars in IBD can be extrapolated from another sensitive indication.

  • As for all biologics, traceability should be based on a robust pharmacovigilance system.


This marks a significant shift from the previous ECCO position paper (2013), which advised that switching from an established biologic to a biosimilar was inappropriate and called for more data on the safety and benefit of biosimilars in general. Professor Silvio Danese, President Elect of ECCO commented: “Findings from the 2015 ECCO survey of IBD specialists found that around 80% of specialists are confident in using biosimilars, compared to 39% back in 2013.”

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Health Canada revises its biosimilar guidance

Health Canada has issued revised guidance for biosimilar developers. One of the changes relates to terminology: until now, Canada’s official term for biosimilars was “subsequent entry biologics” (SEBs) but in the interests of international alignment, the term “biosimilar” is now being officially adopted. Like the US Food and Drug Administration (FDA), Health Canada has also now stated that a determination of similarity will be based on the entire submission (“totality of evidence”). However – unlike the FDA and European Medicines Agency (EMA) – Health Canada will allow sponsors to use a non-Canadian sourced originator as a proxy for the Canadian drug in comparative studies, as long as the suitability of the chosen originator can be demonstrated. In addition, biosimilars manufactured using methodology different from that of the originator may be eligible for approval

Most other revisions are clarifications rather than major policy changes, but they highlight some of the more unique aspects of Canada’s approach to biosimilar regulation:

  • While Health Canada – like the FDA – requires all biosimilar labels to states that the drug is a biosimilar and to include key information from the originator’s product label, Canadian labels must also include the comparative data of the biosimilar versus the originator.

  • Although Canada’s biosimilar reviewers don’t consider the originator’s patents during their review of the application, they will not authorize a biosimilar for market release until they’re assured the originator’s patents have not been infringed.

  • Although Health Canada isn’t responsible for pricing, their view is that determining how biosimilars will fit into the healthcare system is just as important as regulating them.


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Australia’s Biosimilars Awareness Initiative goes live

The Australian Department of Health has launched a new public website for healthcare professionals and patients as the first public outreach of the Biosimilar Awareness Initiative. The Initiative was announced in May 2015 as part of the Pharmaceutical Benefits Scheme Access and Sustainability Package. The aim of the Initiative is to support awareness of, and confidence in, the use of biosimilar medicines for prescribers and consumers.

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November 2016   +

UNITED STATES: FDA approves Amgen’s biosimilar of Humira® (adalimumab)

The U.S. Food and Drug Administration (FDA) has approved Amgen’s biosimilar of AbbVie’s blockbuster Humira® (adalimumab) – the world’s first approval of an adalimumab biosimilar in a highly regulated market. The biosimilar, which has the trade name AmjevitaTM and the non-proprietary name adalimumab-atto, is the fourth biosimilar to be approved by the FDA.* Amjevita was approved for six of Humira’s ten indications; the patents for three other indications – pediatric Crohn's disease, hidradenitis suppurativa, and uveitis – are yet to expire. In addition, Amjevita was approved for juvenile idiopathic arthritis (JIA) in children who are 4 years of age or more; Humira still has a patent covering the treatment of children with JIA as young as 2 years of age. AbbVie has stated that it anticipated Amjevita would be approved, but has made no secret of its intention to retain market exclusivity until 2022. The company is currently involved in a number of court cases with Amgen about the validity of several of Humira’s patents. Lawsuits aside, the earliest Amgen will be able to launch its product is March 2017, due to the required 180-day notice period following FDA approval.

Industry commentators agree that the FDA’s approval of a Humira biosimilar (and its recent approval of a biosimilar of Enbrel®) will trigger an escalation in biosimilar applications. Currently, the FDA is advising companies developing approximately 60 candidate biosimilars based on more than 20 originator biologics. To date, FDA Advisory Committee meetings have been held for each of the biosimilars on a pathway to approval, but the FDA has announced that this will not be necessary in the case of subsequent biosimilars of the same originator.

*Like the other three FDA-approved biosimilars, Amjevita is not designated as "interchangeable" (i.e. able to be substituted for the originator by a pharmacist without prescriber consultation). The FDA’s criteria for an interchangeability licence are still awaited.

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UNITED STATES: Second major US payer drops originators for biosimilars

UnitedHealth has announced that ZarxioTM, a biosimilar of filgrastim, and BasaglarTM, a follow-on biologic* of insulin glargine, will replace their respective originator products, Neupogen® and Lantus®, on its formulary in 2017. The news follows a similar announcement made recently by CVS Health. Industry analyst Ronny Gal anticipated that similar payer decisions could well be forthcoming when other biosimilars arrive on the US market. He noted that, “We are seeing commercial payers making more aggressive steps to control formulary costs” but acknowledged that these changes are being made at a significantly faster rate than analysts had expected.

*Basaglar was not approved via the FDA’s dedicated biosimilars pathway 351(k) and is therefore referred to as a “follow-on biologic”.

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UNITED STATES: New QuintilesIMS report asks “Who will benefit from US biosimilar cost savings?”

A new white paper issued by QuintilesIMS has revealed that patients in the US may not individually benefit from lower priced biosimilars – it will chiefly be payers who benefit. The paper predicts that patients may see <5% of the $25 billion in savings that the Congressional Budget Office expects biosimilars to generate by 2018 because:

  • When savings are conveyed through a decrease in the drug’s list price, patients who pay a flat co-pay may not see any savings.
  • Few patients, if any, will benefit if the savings are conveyed as drug rebates. These are given by manufacturers to pharmacies, pharmacy benefits managers or wholesalers, often in exchange for purchasing the drug at a certain volume.
  • Medicare Part D beneficiaries may actually pay more for biosimilars. Manufacturers are required to offer 50% discounts for patients in the Part D coverage gap, the “donut hole”. But that requirement excludes biosimilars. A group of Medicare policy advisers has recently strongly supported removing this barrier to the wider use of biosimilar drugs.
  • Patients who use an interchangeable biosimilar may see the most savings, as these drugs could be assigned to a lower formulary tier with reduced cost sharing.

These financial concerns are relevant to patients who would have otherwise been treated with an originator biologic; it remains true that the savings made by payers should allow more patients to receive biologic therapy than was previously possible.

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EUROPE: Non-commercial NOR-SWITCH study supports switching to biosimilar infliximab

New data presented at the 2016 United European Gastroenterology (UEG) Week, show that a switch from originator infliximab (Remicade®) to a biosimilar version (CT-P13) does not adversely affect the safety or efficacy of treatment. Sponsored by the Norwegian government, the study involved nearly 500 patients at 40 sites across Norway who had been on stable infliximab treatment for at least 6 months. The results of the NOR-SWITCH study build on a growing body of real-world evidence that supports the safety and efficacy of biosimilar infliximab. Ahead of the announcement of the NOR-SWITCH findings, a white paper offering a framework for interpreting the data was issued by the Global Alliance for Patient Access.

Further new data presented at UEG Week indicated that total cost savings from the use of biosimilar infliximab in 2015 ranged from €1.35 million in Germany to €5.97 million in Spain. The Spanish findings suggested that use of biosimilar infliximab (CT-P13) could allow up to 1,085 extra patients per year to access biologic therapy.

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EUROPE: Infliximab biosimilars are safe, effective, and cheap, UK audit shows

Infliximab biosimilars are safe and effective and could halve the cost of inflammatory bowel disease (IBD) treatment, a report by the UK’s Royal College of Physicians has found. Use of these drugs could cut the cost of an annual course of treatment from around £10,000 (€11,700, $13,000) to around £5,000, the authors said.

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EUROPE: Ireland prepares new biosimilar policy to improve access

The Irish government is developing a policy aimed at increasing the use of biosimilars and helping the industry to expand domestically. Controversy was sparked by the 4-year pricing agreement the government signed in July this year with the industry body, the Irish Pharmaceutical Healthcare Association, mandating an automatic 20% price reduction for originator biologics when a biosimilar version is launched. Opponents claimed that this arrangement made it uneconomic for biosimilars to compete. It is not clear exactly what form the new pro-biosimilars policy will take, but Ireland’s Health Minister, Simon Harris, has indicated that he is looking to “Create the right market conditions that will enable the biosimilar industry to grow”.

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CANADA: New online consumer resource on biosimilars launched in Canada

Arthritis Consumer Experts (ACE), a national organization providing educational services for people with arthritis – has announced the launch of Biosim Exchange – the first dedicated online biosimilars resource for Canadian consumers. The resource will offer regularly updated factual information on the safety and efficacy of biosimilars, regulatory decisions, and reports on public and private health insurance formulary policies. “There is a real need for balanced, evidence-based information on biosimilars.” Cheryl Koehn, Founder & President, Arthritis Consumer Experts, said.

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CANADA: New Canadian forum calls for better access to biosimilar medicines

A new Canadian alliance of drug manufacturers – the Canadian Biosimilars Forum – has issued a call to both policy-makers and health system leaders to embrace the opportunity that biosimilars represent to both patients and to Canadian healthcare. "Biosimilars offer direct benefits to patients while at the same time providing sustained cost reductions to the healthcare system." one of the Forum Co-Chairs said.

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ASIA PACIFIC: Domestic Indian biosimilars market forecast to reach $40 billion by 2030

Following the introduction of a new regulatory policy in India, the domestic biosimilars market – currently worth an estimated $2.2 billion – is expected to grow at an accelerated pace and reach the target of $40 billion by 2030, according to a new forecast released by the Jawaharlal Nehru Institute of Advanced Studies (JNIAS). Indian biosimilars are also expected to command a 20% share of the global market, the report said.

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October 2016   +

GLOBAL: Global pharmaceutical regulators forum proposes principles for indication extrapolation for biosimilars

The International Pharmaceutical Regulators Forum (IPRF) Biosimilars Working Group (BWG)* has released a reflection paper outlining principles that regulators around the world can use for extrapolating indication(s) during the authorization process for new biosimilars. They state that, in the context of biosimilars, the majority of national regulatory agencies (NRAs) agree that extrapolation of indication(s) can be granted on the basis of “totality-of-evidence”.** However, there appears to be no clear consensus on exactly which data should be submitted and how a decision to approve the extrapolation of indication(s) based on those data should be reached. Furthermore, the decision that is reached can differ between NRAs for scientific, legal or regulatory reasons, which may result in additional work for biosimilar developers.

*The IPRF is an international organization based in Switzerland. Their Biosimilars Working Group (BWG) was formed in February 2014 with 32 members from ten countries and three international organizations. The purpose of the working group is to discuss and harmonize the issues and challenges in terms of regulation of biosimilars among IPRF member countries.

**An approach advocated by the US Food and Drug Administration (FDA) and other NRAs, in which regulators consider the totality of the data and information, including structural and functional characterization, nonclinical evaluation, human pharmacokinetic/pharmacodynamic data, and clinical data, including immunogenicity.

Related article> (The reflection paper can be downloaded from this site)

GLOBAL: Call for clinical trials of biosimilars “to become more similar”

A second story regarding international harmonization: leading rheumatologists Jonathan Kay (USA) and John Isaacs (UK) have published a proposal in the official European League Against Rheumatism (EULAR) journal Annals of the Rheumatic Diseases for biosimilar trial design to be internationally standardized. They say that this standardization could be agreed upon and overseen by regulatory agencies around the world, and that introduction of consistency across clinical trials should increase confidence in biosimilars, both within the healthcare community and among patients. Elements to be standardized could include eligibility criteria, primary and secondary endpoints, assays used for pharmacokinetic and immunogenicity assessments, and statistical methodology.

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EUROPE: NICE guidance on biologics will no longer differentiate between originators and biosimilars

The UK’s NICE (National Institute for Health and Care Excellence) has announced that, going forwards, all relevant published guidance that applies to an originator biological molecule will also apply to any licensed biosimilars. All existing guidance on biologics, for which at least one biosimilar is available on the UK market, will be amended to inform stakeholders and the public that the recommendations for the originator molecule also apply to any current and future biosimilar. Recommendations will refer to the INN (international non-proprietary name) and will not differentiate between the originator and biosimilar products. The guidance will also state that treatment should be initiated with the cheapest available product.

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EUROPE: French survey of patients with inflammatory bowel disease reveals limited understanding of biosimilars

A team of researchers in France, who surveyed 1,181 patients with inflammatory bowel disease, found that only 38% of respondents had heard of biosimilars, despite the fact that their condition is increasingly treated with biosimilars across Europe. When researchers asked these 383 people further questions to see what they knew about biosimilars, 47% said they were worried about safety and 40% claimed they were worried about efficacy. Only about 25% of those who were familiar with biosimilars said they didn’t have any concerns, the study found.

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UNITED STATES: FDA approves Erelzi™, a biosimilar of etanercept

The U.S. Food and Drug Administration (FDA) has approved ErelziTM (etanercept-szzs) for all indications included in the label of the originator product Enbrel®, including rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis. Erelzi is the second biosimilar from Sandoz approved in the US through the FDA biosimilars pathway established under the Biologics Price Competition and Innovation Act. The FDA approval follows a unanimous vote (200) by the FDA's Arthritis Advisory Committee in July to recommend use of Erelzi for all of Enbrel’s indications.

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UNITED STATES: Court says Pfizer's infliximab biosimilar doesn't infringe Remicade® patent

Pfizer Inc.’s biosimilar of Johnson & Johnson’s TNF-alpha inhibitor Remicade® doesn’t infringe a patent, a federal court ruled last month, potentially clearing the way for the launch of the infliximab biosimilar onto the US market in October. Johnson & Johnson said it would appeal the decision and affirmed its sales projections.

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UNITED STATES: Names for interchangeable biosimilars may affect pharmacist dispensing habits

Nearly 63% of US pharmacists say they would feel more confident dispensing an interchangeable biosimilar if it shares the same INN (international non-proprietary name) as the brand-name biologic. The survey, which included 781 members of the Academy of Managed Care Pharmacy and the Hematology/Oncology Pharmacy Association, has just been published but was carried out last year. Since then, the FDA has released draft guidelines proposing that originator biologics and their biosimilars should share INNs, but that each should have a unique four-letter suffix. The survey points out that nearly half of the pharmacists preferred the approach that was eventually suggested by the FDA. Whether the agency ultimately adopts its own proposal remains to be seen.

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CANADA: Canada approves etanercept subsequent entry biologic (SEB)

Canada has approved BrenzysTM, its first SEB* version of Amgen’s Enbrel® (etanercept) made by Korean drugmaker Samsung Bioepis. The announcement was made just 2 weeks after the US approved its first etanercept biosimilar, Sandoz’ ErelziTM.

*A SEB (subsequent entry biologic) is the Canadian term for a biosimilar.

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ASIA PACIFIC: Australia's biosimilar substitution policy comes under fire as etanercept biosimilar is "A"-flagged

Australia’s Pharmaceutical Benefits Scheme Committee has announced that it intends to mark the originator and biosimilar versions of etanercept as equivalent in the Schedule of Pharmaceutical Benefits. This "A"-flagging means that, at the point of dispensing, pharmacists are free to opt for either product in all licensed indications that apply to both. The move has attracted criticism from prescribers and other stakeholders who feel that the prescribing clinician should retain control. However, the decision is in line with the stance Australia has maintained for some time regarding biosimilar substitution.

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ASIA PACIFIC: India announces new biosimilar guidelines

Revised guidelines for biosimilar manufacturers have been launched in India, to replace the original 2012 version. The new biosimilars policy, called the “Guidelines on Similar Biologics” was prepared by the Central Drugs Standard Control Organization (CDSCO) and the Department of Biotechnology (DBT). Key changes include: 

  • Clarification on the source of the reference product: if the reference product (originator biologic) is not marketed in India, it can be licensed in any ICH* country (i.e. EU, Japan, US, Canada, and Switzerland).
  • Provision for post-marketing studies: specific post-marketing safety data are required within 2 years of licensing through a pre-defined single arm study (n>200) and should be compared with historical data of the reference product. If immunogenicity is evaluated in clinical studies, it is not mandatory to carry out additional non-comparative immunogenicity assessments in post-marketing studies.
  • Option for waiver of safety and efficacy study: if a product demonstrates biosimilarity in terms of structural and functional properties, in vitro characterization, and pharmacokinetic/pharmacodynamic (PK/PD) markers that are surrogates of efficacy, Phase III clinical trials may be waived and replaced if necessary by an appropriate single-arm study (n≥100) in the most sensitive indication. Wherever the Phase III trial is waived, immunogenicity data should have been gathered in the PK/PD study and will also need to be generated during post-marketing studies.

*International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

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September 2016   +

GLOBAL: New systematic review of global data finds branded and biosimilar TNF-α inhibitors equally safe and effective

A new Johns Hopkins Bloomberg School of Public Health systematic review, published in the Annals of Medicine, has reported that biosimilars for the treatment of rheumatoid arthritis and other autoimmune diseases appear to be as effective and safe as their branded equivalents. Researchers conducted a systematic review of 19 eligible studies (Phase I, Phase III, and observational studies) comparing the original and biosimilar forms of TNF-α inhibitors. The data from these studies indicated that biosimilar drugs have safety and effectiveness profiles that are very similar to those of their branded counterparts. “Our study should reassure clinicians and patients and, importantly, the folks who pay the bills — insurance companies and government programs like Medicare” the authors said. “Hopefully this will encourage the brisk adoption of these products. There is no question that greater competition in this market will benefit patients, prescribers, and society in the long run.”

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GLOBAL: Roche focuses on subcutaneous versions of leading biologics to bolster defense against biosimilar competition

Now that the original intravenous formulation of rituximab (Rituxan®/MabThera®) has reached (or is soon to reach) patent expiry in many markets, Roche is pursuing approval of new indications for its subcutaneous version – which still has several years of patent protection left. They took the same approach with trastuzumab (Herceptin®) in the belief that it will help protect against biosimilar competition and limit sales erosion. Administering biologics under the skin rather than through intravenous infusions can reduce delivery times significantly without compromising efficacy or safety: 7 minutes compared with 2.5 hours for rituximab, and 5 minutes compared with 90 minutes (initial infusion)/30 minutes (subsequent infusions) for trastuzumab.

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UNITED STATES: Leading pharmacy benefit manager CVS drops coverage of two branded biologics in favor of biosimilars

CVS Health Corp. is embracing biosimilars in an attempt to combat rising prescription drug costs. CVS, whose Caremark unit administers drug-benefit plans for employers and insurers, has said that, from 1 January 2017, it will drop coverage of branded filgrastim and insulin glargine and instead cover their licensed biosimilar versions. Best known as a retail pharmacy chain, CVS is also a major player in the pharmacy benefit management industry, overseeing drug spending for US employers, health insurers, and labor unions. The move by CVS is the latest indication that US health insurers and pharmacy benefit managers are eager to reap savings from biosimilars. CVS Chief Medical Officer Troyen A. Brennan said biosimilars are typically priced 10‒15% cheaper than originators but that CVS has negotiated additional discounts. “We want to signal that this biosimilar movement is real,” Dr Brennan said in an interview. “We have big hopes for [biosimilars] to reduce drug costs overall.”

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UNITED STATES: FDA tells Sandoz to resubmit their application for biosimilar pegfilgrastim

Sandoz has received a complete response letter (CRL) from the FDA for their biosimilar pegfilgrastim candidate. This effectively means that the current application has been rejected and more information has been requested prior to resubmission. This will be a blow to Sandoz, which has been highly successful in the biosimilars field to date, and perhaps more widely to other biosimilar manufacturers, just when it looked like regulatory decisions were becoming a little more predictable. However, other companies have received CRLs, notably Pfizer’s new Hospira unit, whose biosimilar version of Amgen’s kidney disease drug Epogen® (epoetin alfa) was rejected last year. It is unclear what the Sandoz CRL refers to, and whether the issues have to do with a clinical trial or manufacturing concerns. In a statement released last year, Sandoz said it had conducted three pivotal clinical trials on its biosimilar: one pharmacokinetic and pharmacodynamic study in healthy volunteers, and two comparative efficacy and safety studies in patients with breast cancer (PROTECT 1 and 2).

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UNITED STATES: AbbVie begins litigation against Amgen over adalimumab biosimilar

Amgen's biosimilar of adalimumab, ABP 501, which was given unanimous support by the US Food and Drug Administration’s (FDA) Arthritis Advisory Committee in July, now faces significant litigation by AbbVie, manufacturer of the originator, Humira®. AbbVie's patent infringement lawsuit against Amgen, which was filed on 4 August 2016 in the US District Court for the District of Delaware, claims ABP 501 infringes 61 of the 100+ patents that cover Humira. Only 10 patent infringements are cited in the complaint at this first stage of the process but AbbVie has promised a second wave of litigation involving dozens of additional patents. The suit also contends that, although Amgen provided its abbreviated biologic license application to AbbVie when the parties began exchanging patent information in February, it did not provide any other information that describes the process or processes used to manufacture ABP 501 as required by the Biologics Price Competition and Innovation Act (BPCIA).

Amgen has been the plaintiff in several suits seeking to protect its branded biologics against biosimilar competitors. It has complaints pending against Sandoz claiming that biosimilars to Neupogen® (filgrastim), Neulasta® (pegfilgrastim), and Enbrel® (etanercept) infringe its patents; a complaint against Apotex Inc. over its Neulasta biosimilar; and a complaint against Hospira Inc. (now Pfizer Inc.) over its Epogen® (epoetin alfa) biosimilar. Amgen’s role is reversed in the Humira litigation, a fact AbbVie highlights in disputing Amgen's arguments. It therefore seems that, although ABP 501 may shortly receive FDA approval, its launch in the US may be subject to significant delay.

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UNITED STATES: The Pharmaceutical Research and Manufacturers of America accepts Teva, a maker of generics, as a member

In a move that underscores the changing landscape of the pharmaceutical industry, the chief US trade group has officially accepted one of the world’s largest generic drug makers into its ranks. Teva Pharmaceuticals has become a member of the Pharmaceutical Research and Manufacturers of America, which has traditionally been a staunch defender of brand-name companies. The decision to accept Teva has surprised some industry watchers, given the historical rivalry between brand-name and generic manufacturers. The move, however, is not all that unexpected, if only because – especially in the biosimilars field – the lines are beginning to blur and the strategic interests of brand-name and generic companies are increasingly overlapping.

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ASIA PACIFIC: Japanese Biosimilars Association launched

The establishment of a dedicated Biosimilars Association has been announced in Japan. Bringing together stakeholders from industry, government, and academia, the association aims to contribute to the country's healthcare by clarifying the optimal role of biosimilars, sharing knowledge and experience, and discussing obstacles to their acceptance.

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EUROPE: Irish government reaches controversial deal with pharma firms on biologic drug prices

A new agreement has been reached between the Irish government and the Irish Pharmaceutical Healthcare Association (IPHA), which has been promised to result in savings of around €750 million. The 4-year deal is intended to facilitate patient access to new and innovative medicines, including biologics. Under the deal, biologic medicines that have lost exclusivity will be automatically discounted by 20% when a biosimilar competitor is launched. In addition to the price cut, suppliers of off-patent biologics must pay the Health Service Executive (HSE) a rebate of 12.5% of the value of the reduced price.

However, the Healthcare Enterprise Alliance (HEA), which represents the generics and biosimilars sector, says the agreement blocks competition, making it uneconomic for biosimilars to enter the market. “The inclusion of an artificial pricing clause that blocks better value biosimilar medicines entering the market is profoundly disappointing,” HEA president Sandra Gannon said. “It leaves Ireland one of the only countries in the world preventing competition in this part of the medicines market. We have seen in recent years what can be achieved by bringing a reforming ethos to medicine prescription, dispensation and pricing. This agreement halts that momentum.” To date, Spain has been the only other European Union country to mandate that manufacturers of originator biologics must drop their prices upon patent expiry.

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August 2016   +

GLOBAL: International Council on Harmonisation includes International Generic and Biosimilars Medicines Association for the first time

On 15 June 2016, the International Council on Harmonisation (ICH; formerly the International Conference on Harmonisation) announced that the International Generic and Biosimilars Medicines Association (IGBA) could join the ICH as an Assembly Member. For the first time, an association representing generic and biosimilar companies is able to sit at the table with regulators and pharmaceutical companies more traditionally on the innovator spectrum.

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USA: FDA Advisory Committees unanimously approve biosimilar candidates of adalimumab (Amgen) and etanercept (Sandoz)

The US Food and Drug Administration’s (FDA) Arthritis Advisory Committee has voted unanimously to support ABP 501, Amgen’s biosimilar of AbbVie’s blockbuster biologic Humira® (adalimumab) and also to grant extrapolation to all Humira’s licensed indications. The vote – 26–0, with no abstentions – followed the release of a positive review from FDA staff. In documents posted on the FDA's website, staff scientists said the data suggested ABP 501 and Humira are "highly similar" in their safety, purity, and potency in treating rheumatoid arthritis and plaque psoriasis. The staff's briefing report stated that Amgen's data also supported use of ABP 501 for other indications that Humira is used to treat. The FDA verdict represents the first regulatory approval for an adalimumab biosimilar within any highly regulated market. However, AbbVie has ensured that Humira is protected by numerous patents, which may prevent the marketing of biosimilar competitors for several years. 

Just a couple of days after the FDA vote on Amgen’s adalimumab biosimilar, Sandoz’s etanercept biosimilar also received unanimous approval from an FDA panel, and a recommendation for full extrapolation (although this product had the advantage of already being approved and licensed in the European Union).  

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USA: Academy of Managed Care Pharmacy launches online Biosimilars Resource Center

The Academy of Managed Care Pharmacy (AMCP) has announced the launch of their Biosimilars Resource Center (BRC), an unbiased, policy-neutral repository of educational resources and information on biosimilars for pharmacists, physicians, nurses, and other healthcare providers. The site was developed in partnership with leading national pharmacy organizations and can be accessed at The BRC provides access to educational tools and training materials on biosimilars, including one-pagers, web-based educational seminars, accredited continuing education, and journal articles. It also includes information about the status of local biosimilar substitution laws within each US State.

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USA: Supreme Court consults Solicitor General on biosimilar launch timing issue

The US Supreme Court has asked the Obama administration’s Solicitor General for their perspective on whether a lower court wrongly delayed Novartis AG's launch of their filgrastim biosimilar ZarxioTM in a case that is being closely watched as a test of the law on biosimilar drugs. In its petition for certiorari, filed in February, Novartis asked the Supreme Court to overturn a ruling by the US Court of Appeals for the Federal Circuit, which ruled it could not launch Zarxio until 180 days had elapsed following FDA approval. Zarxio was approved in March 2015, but not launched until September.

In the meantime, in Amgen’s other lawsuit against Apotex, which concerns a biosimilar of pegfilgrastim, the Federal Appeals Court has again ruled that biosimilar makers must wait until they have an FDA approval in hand before giving the originator manufacturer 180 days’ notice that they intend to launch their product. The court was adamant that the biosimilar law “provides for two stages of litigation” and that drugmakers should get a second chance to make a last stand on patent issues after FDA approval of a biosimilar. The ruling, while settling the question for now, will give the Supreme Court more to think about should it decide to pursue the issue.

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USA: New law proposed to support biosimilar manufacturers gaining access to originator

Four US senators are campaigning for the introduction of the Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act. The Act supports access to originator products for biosimilar development. Biosimilar manufacturers must obtain samples of originator drugs in order to develop and test their products but originator manufacturers often put up barriers by refusing to sell product samples, or impeding participation in FDA-required safety protocols. The CREATES Act would prevent such tactics by authorizing a judge to award damages in cases of this nature and would allow court-supervised negotiations between originator companies and biosimilar developers.

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EUROPE: Italian regulators endorse switching to biosimilars on a case-by-case basis

The Italian Medicines Agency (AIFA), which recently published a major report outlining plans to address the challenge of "sustainable innovation", has now released a new concept paper on biosimilars, which no longer suggests that their use should be restricted to treatment-naïve patients. In the latest paper, AIFA has instead indicated that substitution of originator biologics with biosimilars is a possibility that should be left to the clinical judgment of the doctor involved. AIFA concludes that biosimilars offer a valuable opportunity to develop the competitiveness of the market, and to aid the rationalization of public spending.

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EUROPE: Concern in the Republic of Ireland over "biosimilar blocker deal"

A deal currently being negotiated between the Republic of Ireland Irish Pharmaceutical Healthcare Association (IPHA), which represents the branded drug sector, promises to cut the price of off-patent biologics by 30% when biosimilar competition enters the market. But the Healthcare Enterprise Alliance (HEA), which represents producers of generics and biosimilar drugs, says the 30% threshold makes it uneconomic for them to compete. As a result, without competition, originators will remain at their current higher prices for the period of the agreement. In the cases of Humira®, Enbrel®, and Herceptin®, that amounts to a cumulative price difference of €54 million a year. The HEA has written to Minister for Health, Simon Harris, expressing its concern over what it calls the “biosimilar blocker” clause. It is understood the Minister has yet to respond.

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EUROPE: NHS England takes action to advise physicians on best use of biosimilars, proposing a patient-centered approach

In an effort to ensure optimal and consistent use of biosimilars, NHS England has engaged with local stakeholders who have decision-making responsibility for commissioning, prescribing, dispensing, and monitoring biological medicines, as well as with the Association of the British Pharmaceutical Industry (ABPI), the British Biosimilar Association (BBA) and, importantly, patient representatives. Key considerations raised by physicians in workshop sessions included the need for patients to be involved in decisions about their medication, including the opportunity to discuss any changes to what they are currently prescribed. The importance of appropriate clinical monitoring and collection of real-world evidence following biosimilar prescribing were also discussed. NHS England is working with national partners to develop a toolkit with practical materials and guidance for appropriate local use of biosimilars.

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MENA: Substantial revisions to biosimilar regulatory guidelines in Israel

Israel's Ministry of Health has published substantial revisions to its guidelines for the registration of biosimilars, easing many of the requirements for biosimilar approval. Specifically, the revisions (1) refine requirements for comparative studies with originator biologics; (2) outline an interchangeability policy; (3) relax the extrapolation policy; (4) expand the list of reference countries on which to base a biosimilar application;* (5) introduce labelling requirements; and (6) allow importation of a biosimilar in some cases, where the biosimilar is not registered in Israel. However, the need for pharmacovigilance is highlighted and made more specific in the new version of the guidelines.

*In the former guidelines, a biosimilar had to be previously approved either by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA), in order to be registered in Israel. According to the revised guidelines, registrations in Canada, Australia, New Zealand, Japan, or Switzerland may also constitute a basis for registration in Israel.


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ASIA-PACIFIC: South Korea’s biosimilars industry poised to grow domestically and abroad

According to the Korean Pharmaceutical Manufacturers Association, the biosimilars market in South Korea will grow to 150 billion won (approximately USD $130 million) by 2019, nearly double its 2013 value. Six biosimilars have been approved in South Korea since 2012, and many others are currently in the development pipeline. Contributors to the domestic market’s rapid growth, are the South Korean government’s support of the biosimilars industry, as well as major investments in biosimilar development by companies like Celltrion and Samsung Bioepis. South Korea hopes that its share of the global market for biosimilars will grow similarly rapidly, with a goal of controlling 22% of the market by 2020. In support of this goal, the South Korean government has invested heavily in domestic biopharmaceutical companies by providing substantial capital and regulatory assistance.


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July 2016   +

GLOBAL NEWS: New reports from Hong Kong and Italy spell out the far-reaching benefits of introducing biosimilar G-CSF

Separate reports from Hong Kong and Italy have revealed the positive impact of granulocyte-colony stimulating factor (G-CSF) biosimilars on patient care and healthcare budgets. Dr Stephen L Chan at the Department of Clinical Oncology, Chinese University of Hong Kong explains that, although his center has always aimed to comply with the American Society of Clinical Oncology (ASCO) recommendation that patients at ≥20% risk of febrile neutropenia should receive G-CSF prophylaxis, this practice was hindered in the past by the cost of filgrastim, which was listed as a self-financed item for many indications. However, since the introduction of filgrastim biosimilars into the public healthcare system in Hong Kong:

  • the price of the originator has come down by 40–60%
  • prophylactic use of G-CSF has increased by approximately 20%
  • the reduced cost pressure has allowed individual patients to opt for their preferred cancer treatment regimen (which may otherwise have been too expensive)
  • the reduced cost burden has freed up healthcare budgets.

Meanwhile a new report from Italian researchers has shown that, within five Italian centers, the overall use of G-CSF increased by 38% in the 5 years from 2009 to 2014, driven by the introduction of filgrastim biosimilars. The authors comment that, in the year 2014 alone, when biosimilar filgrastim accounted for almost 70% of all G-CSF use, a saving of €280,000 would have been achieved if only one-third of originator product users had used biosimilar filgrastim instead.

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GLOBAL NEWS: Positive Phase III results announced for Mylan and Biocon’s trastuzumab biosimilar

A biosimilar of trastuzumab, jointly developed by Mylan and Indian biotech firm Biocon, has achieved positive results in its Phase III clinical study – the first results of this kind for a trastuzumab biosimilar. In the HERITAGE Study (n=500) – which was presented at ASCO – the biosimilar candidate, Myl-14010, was shown to be essentially equivalent in safety and effectiveness to Roche’s Herceptin®, which has transformed the outlook for about 25% of breast cancer patients over the past two decades. Richard Schilsky, MD, ASCO Chief Medical Officer, commented: “This is a very well-conducted prospective, randomized, non-inferiority study that shows that overall response rates for the biosimilar are similar when both drugs are given with chemotherapy, as they would typically be given in clinical practice.” Mylan and Biocon are believed to be on track to file for approval for Myl-14010 in both the European Union and the United States in 2016/2017.

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GLOBAL NEWS: 90% of doctors worldwide are receptive to prescribing biosimilars, although many want more information

SERMO, the leading global social media network exclusively for doctors, has announced the results of a biosimilars poll involving 3849 physicians from 28 countries worldwide:

  • 47% said they believe biosimilars will prove safe and effective enough to prescribe
  • 43% said they would need more educational information on biosimilars before prescribing them
  • 10% said they would not prescribe biosimilars, even if provided with more educational information about safety and effectiveness. 

Although some quotes from physician interviews revealed a wide range of misconceptions about biosimilars and their approval requirements, the findings indicate that 90% of those polled are receptive to prescribing biosimilars, even if many would like more information and education first.

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GLOBAL NEWS: Even engaged patients with relevant diagnoses have low awareness of biosimilars

An international survey conducted to understand the levels of awareness, usage, and knowledge of biosimilars among patients, caregivers, and the general population in the EU and US (n=3198) has shown that – even among patients with relevant diagnosed conditions* who have participated in patient support groups – awareness of biosimilars stands at only 20–30%. Among the general population (18–64 years of age), awareness was a mere 6%. Gaps in knowledge about biosimilars included safety, efficacy, and how to gain access to them. One important factor that apparently influences patients’ willingness to try a biosimilar is the reputation of the manufacturer. Similarly, the Sponsor conducting a clinical trial is also a factor influencing a patient’s decision to participate.

*Inflammatory bowel disease including Crohn’s disease and ulcerative colitis, rheumatoid arthritis, psoriasis, breast cancer, lung cancer, colorectal cancer, or non-Hodgkin’s lymphoma.

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EUROPE: Further positive data on patients transitioned from originators to biosimilars

Samsung Bioepis has presented data at the 2016 European League Against Rheumatology (EULAR) Annual European Congress of Rheumatology, showing that, in patients transitioned from Enbrel® to the biosimilar etanercept Benepali®, there were no treatment-emergent safety or immunogenicity issues, and efficacy was sustained for up to 2 years. Similar safety, immunogenicity, and efficacy were also demonstrated in patients transitioned from Remicade® to Samsung Bioepis’ infliximab biosimilar Flixabi® (78-week follow-up). Additional data presented at the congress showed sustained and similar efficacy, safety, and immunogenicity profiles over 52 weeks in patients who transitioned from Humira® to SB5, Samsung Bioepis’ adalimumab biosimilar candidate.

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EUROPE: Dutch Health Minister announces national system to monitor biosimilar switches

Foreseeing an increase in the number of biosimilars that will be available in Europe, the Dutch Minister of Health has announced a new system to track biosimilar use and instances of switching that occur between originator products and biosimilars. The Netherlands Pharmacovigilance Centre Lareb will provide support in setting up the system later this year and will begin monitoring patients who are prescribed biologics at five separate hospitals. Lareb plans to use the information obtained to craft a proposal for a national system to support safe switching to biosimilars, in the interests of a more sustainable Dutch healthcare system. The Dutch Medicines Evaluation Board previously held the view that patients should stay on originator products if they have shown good clinical response. However, in March 2015 it announced that, based on recent experiences with biosimilars, there is enough evidence to support transitions to these products within clinical practice, provided that patients are properly monitored.

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EUROPE: New edition of the "Biosimilar Medicines Handbook" published

The Biosimilar Medicines Group has published a new edition of their publication, Biosimilar Medicines Handbook, which provides a wealth of updated information on the current progress of biosimilar medicines in the EU. The first edition of this guide was published in 2007 when only five biosimilar medications had been approved in Europe, and the landscape was in its infancy. This update focuses on the current marketplace, in which more than 20 biosimilar medications have been approved and launched since 2006, and where the regulatory environment has undergone significant development in the past decade. Click here to download the publication.

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ASIA PACIFIC: Roche files lawsuit in India over proposed bevacizumab biosimilar

Swiss biotech company Roche is suing the Drug Controller General of India (DCGI) and Hyderabad-based Hetero Drugs over the approval process for a proposed biosimilar of bevacizumab. Roche, who markets Avastin® (originator bevacizumab), has argued in the Delhi High Court that Hetero's drug has not been demonstrated to be a true biosimilar of bevacizumab (according to International standards) and therefore should not be allowed to use the name ‘bevacizumab’ or the term ‘biosimilar’. It further maintained that the DCGI had not followed the required process before granting approval of Hetero Drugs’ product.

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June 2016   +

GLOBAL: Two-thirds of biopharma companies surveyed currently market or plan to market biosimilars

A new report entitled Biosimilars Manufacturing: Key Considerations and Expected Outsourcing Practices (3rd edition), from Industry Standard Research (ISR), indicates that the majority of companies who develop and market biologics plan to enter – or are already involved in – the biosimilars market. "We saw a considerable shift from last year's data where 54% of respondents mentioned their company had no plans to develop and market biosimilars; this year just 36% of respondents reported the same," explained Kate Hammeke, Director of Market Research at ISR. She added that this reconsideration on the part of many companies may have been influenced by the US FDA having joined other leading regulators in beginning to approve biosimilars. The findings show that the development and commercialization of biosimilars and innovator biologics no longer fall within two separate ‘camps.’

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EUROPE: Medicines for Europe celebrates 10 years of biosimilars in the European Union

Medicines for Europe and its subgroup, the Biosimilar Medicines Group, are celebrating 10 years of positive patient treatment experience and access to better health thanks to biosimilar medicines. They have announced that:

  • Between 2006 and 2014, biosimilar medicines have increased patient access by 44% overall in the EU-5 countries
  • Since the first biosimilar medicine was approved and marketed in 2006, EU-approved biosimilars have generated more than 400 million patient-days of positive clinical experience.
  • Across Europe, nearly 90% of doctors now know what biosimilar medicines are and nearly 60% have already prescribed them.

However, it has been stressed that the full potential of biosimilars will not be realized unless appropriate policy measures in support of biosimilar uptake are put in place, including clear statements by regulatory agencies on interchangeability, more information for patients and prescribers on the benefits and the underlying science of biosimilar medicines, and policy incentives for hospitals and prescribers to use biosimilar medicines more frequently.

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EUROPE: Limited clinical data may be possible for EU approval of biosimilars of simpler protein products with validated PD markers

As more experience is gained with biosimilars, along with the use of sensitive analytical tools, it is possible that the amount of clinical trial data needed to support an EU biosimilar application for simpler biologics – especially when supported by pharmacodynamic (PD) biomarkers – may be reduced. Moreover, the concept of extrapolation of indications is gaining more credence, and the idea of immunogenicity as a particular problem with biosimilars is becoming questionable. These were among the views put forward at a recent conference organized in London by Medicines For Europe's Biosimilar Medicines Group, where speakers looked at issues regarding biosimilar preclinical, clinical and quality data requirements, extrapolation and immunogenicity, and examined how far the EU regulatory requirements have evolved over the past decade. In the discussion that followed, Peter Richardson, head of quality at the EMA, agreed that after a “slightly conservative approach” at the beginning, “we are now getting to the meat of what we can do with biosimilars and we will see how much we can reduce the clinical trial requirements.” He added, “We have gone a long way but we still need a little bit of caution.”  

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EUROPE: France relaxes its position on biosimilar switching

The French regulatory agency ANSM has relaxed its stance on biosimilar interchangeability to state that, while patients should preferably not be switched between an originator biologic and a biosimilar during their course of treatment, this can be done provided the patient agrees and their treatment is closely monitored. The move represents a clear if subtle shift from ANSM’s 2013 position statement when it said it was "not recommended" to modify the initial prescription by substituting one biologic medicine with another once treatment has begun because "multiple or frequent changes" among similar biological medicines could expose the patient to a higher risk of immunogenic response and make it difficult to monitor side effects, particularly those of immune origin. But the data and knowledge gathered on biosimilars in the intervening years seem to have led the agency to change its mind. In an updated position statement published 3 May, ANSM says that, while it is "not desirable" to modify the initial prescription, in light of the growing body of experience and knowledge of the efficacy and safety of biosimilar medicines in the EU, “a position that formally excludes all interchangeability during a course of treatment no longer seems justified.” 

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EUROPE: British Biosimilars Association launched

A new industry body, the British Biosimilars Association, has been launched with the sole focus of increasing the understanding and use of biosimilar medicines in the UK, which currently lags behind other European countries in its uptake of biosimilars. Forming a sector group of the British Generic Manufacturers Association (BGMA), the body will focus on ensuring that patients can benefit from access to potentially life-saving biologic medicines to the same extent that they do in elsewhere in Europe. Keith Ridge, NHS England’s chief pharmaceutical officer, says, “We very much welcome the creation of the British Biosimilars Association with its clear focus on providing information about these vitally important medicines. Biosimilars have enormous potential to deliver increased patient access as well as savings to the NHS which can be reinvested elsewhere.”

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EUROPE: European physicians want more detail in biosimilar package inserts

European physicians would like biosimilarity data included in the package insert for each licensed biosimilar product, according to a survey by EuropaBio. In the EU, package inserts for biosimilars and their originator products are in many instances almost identical (following the approach for generic medicines) despite different data requirements for the approval of biosimilars and generics. Among the 210 physicians surveyed in seven EU countries, 87% said it would be helpful, or very helpful, to include product-specific biosimilarity data in package inserts. 

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USA: ZarxioTM, the first US biosimilar, reaches 1-year anniversary

6 March marked the 1-year anniversary of the first biosimilar approved in the US via the FDA’s dedicated 351(k) pathway. Novartis’ Zarxio™, a biosimilar of Amgen’s Neupogen®, won approval in March 2015, ushering in a new source of competition for branded biologic drugs in the US. Uptake of Zarxio was initially modest but it did increase subsequently, based on information from a survey of 61 US oncologists. Initially most respondents had said that they would not use Zarxio for several months after its US launch but it has now been revealed that every single oncologist surveyed had prescribed Zarxio to at least one patient by 6 months post-launch.

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USA: US payers encouraged to incentivize prescribers to choose biosimilars

Incentives for physicians to prescribe biosimilars could increase utilization and reduce costs, according to a new report, Payor Strategies to Promote Biosimilar Utilization, issued by the Pharmaceutical Care Management Association (PCMA). The report notes that, “Policymakers and payors could, in a manner similar to how some payors promote increased generic utilization, encourage physicians to use biosimilars, by rewarding them for doing so.” 

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CANADA: Pan-Canadian Pharmaceutical Alliance unveils new principles for price negotiation on biologics

Manufacturers of originator biologic products and biosimilars are set to come under greater pressure to lower prices in Canada. In order to win reimbursement they will likely have to enter into pricing talks with the pan-Canadian Pharmaceutical Alliance (pCPA), which negotiates drug prices on behalf of Canada's public provincial and territorial drug plans. In a bid to develop a more competitive and transparent market for biosimilars, the pCPA has published its First Principles, aimed at guiding consistent negotiations for both biosimilars and their originator products. 

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ASIA-PACIFIC: Indian court reluctantly backs two trastuzumab biosimilars

Despite grave doubts, an Indian high court judge is allowing two drugmakers to produce and market contested biosimilars of Roche’s breast cancer therapy Herceptin®. In a temporary injunction, Justice Manmohan Singh of the High Court of New Delhi permitted Biocon and Mylan N.V.’s Indian subsidiary to launch its biosimilars of Roche’s trastuzumab in India, although he openly questioned the legitimacy of the approval of the two biosimilars, noting that both candidate drugs were submitted for approval without the usual clinical data requirements, and that they were granted approval within only 5 days, despite having to navigate three regulatory committees. Singh acknowledged that his hands were tied because only the Central Licenses Approving Authority has the power to suspend or cancel biosimilar approval. Nevertheless, Singh’s interim order prohibits Biocon and Mylan from referring to their products as biosimilars or otherwise linking them to Herceptin in labelling or promotions. Mylan has said it intends to appeal the labelling restrictions.

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May 2016   +

GLOBAL: Major new report predicts potential savings from biosimilars of $56–110 billion over next 5 years

Greater acceptance of biosimilar medicines in a growing number of therapy areas and an active biosimilar research and development pipeline in many countries are expected to deliver total savings of between $56 and $110 billion (€49–98 billion) across Europe’s top five markets and the United States through 2020, according to new research released today by the IMS Institute for Healthcare Informatics.

These estimates are based upon the fact that, by 2020, eight major biologics are expected to lose exclusivity protection, including those used to treat autoimmune disorders and diabetes. If the average discount offered with a biosimilar of each product is 20%, the total saving is predicted to be $56 billion, projected to rise to $110 billion if average discounts of 40% are secured. The report points out that savings will also depend on policy decisions made and actions taken around incentives and stakeholder education. They state that health systems best positioned to capitalize on the benefits of biosimilars are those that support functioning competitive markets – where manufacturers are motivated to participate over the long term, and where physicians are at the heart of the decision-making process. The full report, including a detailed description of the methodology, is available at

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UNITED STATES: FDA approves InflectraTM – second licensed US biosimilar

On April 5, 2016, the U.S. Food and Drug Administration (FDA) approved Celltrion’s InflectraTM, a biosimilar of infliximab, which has been given the generic name infliximab-dyyb. As in the EU, the approval of Inflectra – which was based on data in rheumatoid arthritis – was extrapolated to include all the clinical indications of the originator Remicade®, including ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis. Celltrion Chief Executive, Kim Hyoung Ki, expects Inflectra to be priced approximately 20–30% lower than Remicade in the US market, but the final price will be decided after discussions with partner Pfizer. Inflectra was approved by the European Medicines Association (EMA) in 2013 and began sales in Europe’s largest countries in February 2015, gaining more than a 20 percent share of the Remicade market in terms of patient numbers as of December 2015. But obstacles to the US launch remain: Johnson & Johnson (which markets Remicade in the US) asserts that Inflectra infringes on a Remicade patent that doesn't expire until September 2018 and vows to defend its intellectual property rights.

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UNITED STATES: The American College of Rheumatologists welcomes biosimilar infliximab

In response to the FDA approval of InflectraTM, a statement has been released by the American College of Rheumatologists (ACR). Joan Von Feldt, MD, the group’s President says: “The safe adoption of biosimilars into the US marketplace remains a top priority for the ACR. Biologics are a lifeline for patients living with rheumatic disease, helping many to avoid pain, long-term disability and life-threatening complications. Unfortunately, many of our patients struggle to afford these complex therapies due to their high cost.” She continues, “The ACR welcomes the introduction of biosimilars to the US healthcare system and is hopeful that the decrease in cost resulting from the availability of safe and effective biosimilars in the US will increase our patients’ access to life-changing therapies and improve their overall health.”

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UNITED STATES: National Comprehensive Cancer Network (NCCN) announces its support for biosimilars

At the Annual Meeting of the National Comprehensive Cancer Network (NCCN) in Hollywood, Florida, USA, Andrew D Zelenetz, MD, from the Memorial Sloan Kettering Cancer Center, took to the podium to present the NCCN’s position on biosimilars. Dr Zelenetz told the audience that the industry and other stakeholders are paying increased attention to understanding how biosimilars can replace expensive originator biologics. He announced that the amount spent on oncology biologics in 2014 touched $28 billion, adding that “the extremely high prices of most biological products have forced us to look for options”. Dr Zelenetz pointed out that biosimilars may yield 20–40% discount and stated that they “should be added as an alternative to the originator product”.

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UNITED STATES: American College of Physicians recommends removing obstacles to biosimilar access

The American College of Physicians (ACP) has published a new policy paper, Stemming the Escalating Cost of Prescription Drugs, in the Annals of Internal Medicine. Among a number of recommendations, the ACP states that “unresolved policy issues need to be addressed to ensure safe use of approved biosimilars and maximum utilization of biosimilars by patients and physicians.”

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UNITED STATES: Updated FDA labeling guidance calls for “biosimilarity statement”

About a year after the FDA approved the first US biosimilar, it has released new draft guidance on how biosimilars should be labeled. The guidance differs from the labeling the FDA approved last year for Sandoz’s ZarxioTM, a filgrastim biosimilar. While Zarxio’s labeling mirrors the originator biologic and makes no reference to the product being a biosimilar, the new guidance recommends inclusion of a “biosimilarity statement” following the approval date. Had the statement been used on Zarxio’s label, it would have read: “ZARXIO (filgrastim-sndz) is biosimilar to NEUPOGEN (filgrastim) for the indications listed.”

The guidance also recommends that the following footnote for “biosimilar” appear at the end of the highlights section before the revision date: “Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product.” However, the FDA says the clinical data included on the label should still be that of the originator product, with no need to include the data demonstrating biosimilarity.

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CANADA: Apobiologix launches filgrastim SEB (subsequent entry biologic; the Canadian term for biosimilar)

GrastofilTM, a SEB (subsequent entry biologic) of filgrastim, has been launched in Canada by Apobiologix, a Division of Apotex Inc. Like Sandoz’s ZarxioTM (the first US biosimilar), Grastofil is a biosimilar of Amgen’s Neupogen®. Its approval by Health Canada last year brought the number of licensed SEBs to four.

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ASIA PACIFIC: Japanese regulators approve insulin glargine biosimilar from Indian manufacturer Biocon

Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved a biosimilar of insulin glargine made by India’s Biocon Ltd. Biocon’s product – which is named Basalog® – is expected to be launched in Japan in Q1 2017. Japan is the second largest insulin glargine market in the world with a value of US $144 million and already has an insulin glargine biosimilar marketed by Lilly and Boehringer Ingelheim. However, the launch of Basalog is notable, because achieving approval in Japan – which is considered a highly regulated market – is a significant achievement for an Indian manufacturer, and one which Biocon itself describes as a “huge credibility milestone”.

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April 2016   +

GLOBAL: First consortium of local manufacturers to make affordable biosimilars available for low-income countries

The WHO, with the support of Utrecht University in the Netherlands, has brought together local manufacturers in low-income countries to collaborate on developing a biosimilar of a much-needed biologic for the lowest possible price. The drug, called palivizumab (Synagis®), protects against lung disease caused by respiratory syncytial virus (RSV). According to the WHO, infection with this virus is the second most common cause of death in children up to 1 year of age in low-income countries. Four companies, mAbXience, Libbs, Medigen and SPIMACO, signed a contract for production of a palivizumab biosimilar with Utrecht University and the WHO on 9 March 2016. “This is the first time that commercial parties in low-income countries will deal with a global health issue on their own,” explains project founder and Professor of Pharmaceutical Biotechnology at Utrecht University, Huub Schellekens. By sharing the development costs, the companies in the consortium will be able to offer the drug for a much lower price than usual.

Having recognized the need for the product, the WHO went looking for a university that had the biotechnological expertise to produce the biosimilar and was willing to transfer that knowledge. They chose Utrecht University’s Department of Pharmaceutical Sciences in part because of its leading position in the field. Utrecht University in turn set up the UCAB Foundation to implement the project. The biosimilar for palivizumab will be developed by UCAB and the pharmaceutical company mAbXience (a subsidiary of the international pharmaceutical firm Chemo). They will then transfer the necessary technology and knowledge to the other partners in the consortium. UCAB will also arrange for the drug to be approved for release to market in the low-income countries. The drug will be named Lunamab, after Prof. Huub Schellekens’ granddaughter Luna. He expects that the drug will be available on the market in the first countries by late 2017.

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GLOBAL: Greater prescriber confidence in biosimilars in both the EU and US, according to new surveys

According to a new US survey, nearly 50% of clinicians in five major specialty areas (dermatology, endocrinology, gastroenterology, oncology, and rheumatology) anticipate expanding their prescribing of biosimilars in the next 3 years, as biosimilar availability increases. Reflecting practical considerations, 25% of respondents said that payers and insurance firms will ultimately determine – if not mandate – their level of biosimilar prescribing and 17% felt biosimilars would become the norm, replacing originator biologics in the next 3 years. InCrowd's MicroSyndicated survey captured data from 150 US-based board-certified physicians in specialties where biologics prescribing is significant. The survey results indicate a clear shift in US prescriber attitudes to biosimilars, which were generally viewed with doubt and suspicion only 2 or 3 years ago.

Meanwhile in Europe, members of the European Crohn's and Colitis Organization (ECCO) who prescribe infliximab for inflammatory bowel disease were asked about their views on the biosimilar versions that have been available since 2014 (RemsimaTM and InflectraTM*). The survey found that 44.4% of prescribers consider the biosimilars interchangeable with the originator product Remicade® – a stark contrast to the mere 6% who felt that way when surveyed in 2013. Only 19.5% of respondents said they had little or no confidence in the use of biosimilar monoclonal antibodies, down from 61% who gave that response in 2013.

*Remsima and Inflectra are the brand names of a Celltrion infliximab biosimilar known as CT-P13. They are identical products but separately marketed.

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GLOBAL: Real world studies in nearly 600 patients – including children – confirm efficacy and safety of infliximab biosimilars in IBD

Delegates at the European Crohn’s and Colitis Organisation (ECCO) congress in Amsterdam have heard that ten real-world studies involving nearly 600 patients with IBD in eight countries have all shown comparable efficacy and safety following a switch to biosimilar infliximab* from the originator Remicade®. In addition, a new publication in the Journal of Crohn’s and Colitis reports the same outcome in a switching study in 39 children. In Europe RemsimaTM and InflectraTM are already approved for IBD on the basis of indication extrapolation from data in rheumatoid arthritis (RA). 

In the US, biosimilar infliximab (CT-P13*) has been strongly recommended for approval by an FDA advisory committee and a final FDA decision is awaited. As in Europe, the recommendation included approval of an IBD indication based on extrapolation of RA data. Switching data were included in the application for CT-P13.

*Celltrion’s infliximab biosimilar known as CT-P13 is marketed under the two brand names Remsima and Inflectra.

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UNITED STATES: US Supreme Court petitioned on 6-month biosimilar launch delay

Novartis' Sandoz has called on the US Supreme Court to review a lower court ruling that found biosimilar makers must wait an additional 6 months after FDA approval before they can bring their product to market. The petition for the Supreme Court’s review relates to Sandoz’s ZarxioTM (filgrastim-sndz), which came to market as a biosimilar version of Amgen’s Neupogen (filgrastim). Although the FDA approved Zarxio in March 2015, the product did not actually come to market until September because of a Federal Circuit ruling on a provision in the Biologics Price Competition and Innovation (BPCI) Act. Sandoz argues that the Federal Circuit turned this mere notice provision into a grant of 180 days of additional exclusivity for all biologics beyond the period Congress expressly stipulated, delaying the launch of all future biosimilars by 6 months. They added that lower courts are already using the appeals court decision to grant or consider injunctions against biosimilars, circumventing Congress' desire to lower the cost of medicines and make them available to prescribers and the patients who need them as soon as possible. 

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UNITED STATES: FDA launches continuing education program on biosimilars

The FDA has launched a new continuing education program to help healthcare providers gain a better understanding of biosimilars. The eight-module course covers a wide range of topics, from the 2009 Biologics Price Competition and Innovation (BPCI) Act to the manufacturing process for biosimilars and regulatory requirements for approval. The program is available on the course website at For US physicians, it also includes 1.5 hours of AMA PRA Category 1 CE credits valid through February of 2019. 

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UNITED STATES: Originator companies may be using REMS to restrict generic/biosimilar competition

It has emerged that, as well as patent lawsuits and formulation changes to their products, biologic originator manufacturers may be leveraging an additional potential barrier to biosimilar competition. By using Risk Evaluation and Mitigation Strategies (REMS) – required by regulators in the case of many originators to ensure that products with potentially dangerous side effects are distributed and administered safely – originator manufacturers are attempting to stop competitors from buying the originator supplies needed to develop generic or biosimilar versions. A study carried out for the Generic Pharmaceutical Association in 2014 estimated that REMS were used to protect USD $5.4 billion in sales on 40 small-molecule drugs that had reached patent expiration. About 40% of FDA-approved drugs are now subject to REMS and the impact on biosimilar development could be significant.

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EUROPE: EMA follows FDA in accepting application for pegfilgrastim biosimilar

We reported in January of this year that the FDA has accepted an application from Sandoz for a biosimilar of pegfilgrastim (Neulasta®), a PEGylated form of the recombinant human granulocyte colony-stimulating factor (GCSF) analogue filgrastim, which is used in patients receiving cancer chemotherapy who are at risk of neutropenia-related infection. Now the EMA has accepted this application too.

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EUROPE: British Society of Gastroenterology endorses use of biosimilar infliximab in IBD

New guidance on the use of biosimilar infliximab in inflammatory bowel disease has been issued by the British Society of Gastroenterology (BSG). Dr Barney Hawthorne, chair of the IBD committee at the BSG, said, “The biosimilar infliximab CT-P13* – RemsimaTM or InflectraTM – has been in wide use for IBD treatment and there is a rapidly growing literature confirming its safety and efficacy. Our new guidance confirms that there is sufficient experience with this drug to use it both for new patients requiring anti-TNF therapy, but also to consider switching existing patients on Remicade® to Remsima or Inflectra. This would be appropriate for patients who have responded well to infliximab, are in a stable clinical state, where there is appropriate support for patients, with their agreement and in keeping with NICE recommendations on biosimilars.” The new recommendations have been welcomed by UK healthcare professionals. “Guidelines from professional groups such as the BSG are crucially important in providing confidence for clinicians and patients in the use of biosimilar medicines in the UK,” said Dr Fraser Cummings, Consultant Gastroenterologist at University Hospital Southampton.

*Celltrion’s infliximab biosimilar known as CT-P13 is marketed under the two brand names Remsima and Inflectra.

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EUROPE: The European Generic and Biosimilar Medicines Association becomes ‘Medicines for Europe’

‘Medicines for Europe’ is now the new name of The European Generic and Biosimilar Medicines Association. Representing the pharmaceutical companies supplying the largest share of medicines across Europe, Medicines for Europe is the voice of the generic and biosimilar medicines industries in Europe. The organization states that their industries supply the majority of Europe's prescription medicines, estimated to grow substantially in volume over the next 5 years. The repositioning of the association as Medicines for Europe aligns with their aim of improving patient access to modern medicines and providing solutions for the sustainability of European healthcare systems.

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March 2016   +

UNITED STATES: FDA Advisory Committee strongly backs approval of infliximab biosimilar RemsimaTM

An Advisory Committee to the US Food and Drug Administration (FDA) has voted 21–3 to approve RemsimaTM, a biosimilar of infliximab, which – like all biosimilars – would be available at a discount compared with the originator. Although the FDA is not obliged to follow the advice of the Advisory Committee, not doing so is rare. If approved, Remsima will be the second biosimilar approved via the dedicated 351(k) pathway after Sandoz’ ZarxioTM, which was approved in March 2015.

The FDA Advisory Committee determined that clinical trials of Remsima showed no clinically significant differences compared with the originator Remicade® in the treatment of rheumatoid arthritis and ankylosing spondylitis. Moreover, the panel agreed it was appropriate to extrapolate the license for Remsima to include other Remicade indications, such as psoriasis and inflammatory bowel disease.

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UNITED STATES: FDA accepts Amgen’s adalimumab biosimilar application for review

The FDA has accepted Amgen’s application for ABP 501 (a biosimilar of adalimumab) for review, which was originally submitted to the agency in late November 2015. Phase 3 comparative efficacy and safety studies were conducted in both moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis. The FDA’s acceptance of the application does not, however, indicate any developments with regard to AbbVie’s plans to protect and defend the various patents associated with their originator Humira®. AbbVie remains confident that legal hurdles will keep biosimilar competition at bay for many years.

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UNITED STATES: Biosimilars Forum launches "Partnership for Biosimilars Education and Access"

The Biosimilars Forum* – a non-profit organization dedicated to expanding patient access to biosimilars in the United States – has announced the launch of a new educational initiative, Partnership for Biosimilars Education and Access. The project will focus on raising awareness and promoting access to biosimilars throughout the US. In support of the initiative, the Biosimilars Forum has released two educational guides designed for healthcare professionals, media, and patient advocacy organizations to learn more about biosimilars. The information is free and available at

*The founding members of the Biosimilars Forum represent the majority of companies with the most significant US biosimilar development portfolios.

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UNITED STATES: FDA inundated with biosimilar applications

Janet Woodcock, Director of the FDA's Center for Drug Evaluation and Research, has told members of a governmental health subcommittee that she is worried about the agency's ability to manage what she expects will be an increasing number of biosimilars applications. "What I'm concerned about is that this program is going to explode", said Woodcock. As of January 21, 2016, a total of 59 proposed biosimilar products for 18 different originator products were enrolled in the agency’s Biosimilar Product Development (BPD) Program.

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CANADA: Canada revises its guidelines for subsequent entry biologics (SEBs)

Health Canada has issued a revised draft guidance document on the submission requirements for subsequent entry biologics (SEBs) – the Canadian term for biosimilars. The updated draft contains a new policy statement about what is required for SEB designation and a new definition of indication extrapolation. It also clarifies what requirements in the guideline are desirable/advisable and which are obligatory. Once comments on the draft have been addressed, the new guidance will replace the previous version of March 5, 2010.

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EUROPE: UK’s NICE endorses biosimilars in new rheumatology guidelines

The UK’s National Institute for Health and Care Excellence (NICE) has issued new guidance on the management of severe rheumatoid arthritis, in which it gives official endorsement to seven originator biologics and – for the first time in a clinical guideline – two biosimilars (RemsimaTM and InflectraTM, both biosimilars of infliximab). Importantly, NICE says treatment should be started "with the least expensive drug", taking into account administration costs, the dose needed, and the price of the drug per dose, suggesting there will be pressure on NHS prescribers to opt for the biosimilars first line.

NICE has also brought out clinical recommendations for ankylosing spondylitis, which again include the two infliximab biosimilars, Remsima and Inflectra. It is notable that the last iteration of this guideline (2008) did not include any infliximab product on cost grounds.  According to Napp, who markets Remsima in the UK, this change was possible because, for the first time, the acquisition cost of the drug was taken into account instead of only its list price, and biosimilars “have been made available at significant discounts through the regional tendering processes”. This is another example of biosimilars driving greater patient access to previously restricted products.

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EUROPE: Norway secures 47% discount for first etanercept biosimilar, Benepali®

Following the approval of Europe’s first etanercept biosimilar, Benepali®, it has been announced by the Norwegian Medicines Agency that Benepali will be sold in Norway at a 47% discount compared with the originator Enbrel®. Benepali is expected to be purchased by most of the country’s state-run hospitals and pharmacies. Norway is known for securing unprecedented biosimilar discounts – in particular, a 72% discount for the infliximab biosimilar RemsimaTM compared with originator Remicade®. While Norway remains an “outlier” compared with elsewhere in Europe, its activities are the focus of great interest in the rest of the EU and beyond.

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ASIA-PACIFIC: Japan announces plan to reduce biosimilar and generic drug prices 

Japan’s Ministry of Health, Labor and Welfare* has proposed a plan to lower prices of generic and biosimilar drugs across its pharmaceutical industry. Under the proposed plan, biosimilars will be initially priced at a 30% discount relative to the originators. The plan is part of a government initiative to increase the overall market share of generic and biosimilar drugs to levels approaching those typically seen across Europe and the US.

*In Japan, which has National Health Insurance, drug price reimbursement is controlled by the Ministry of Health, Labor and Welfare. Every 2 years it adjusts the price of drugs, based on actual market prices charged by wholesalers, and these are almost always reduced. For drug companies, a price cut tends to be offset by increases in volume. In Japan, doctors sell the drugs themselves and tend to make much of their income from this practice.

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February 2016   +

GLOBAL: Successful switching from originator to biosimilar reported in largest real world study to date

Data from the PRospective Observational cohort Study on patients with inflammatory bowel disease (IBD) receiving Therapy with BIOsimilars (PROSIT-BIO), in patients with ulcerative colitis (UC) or Crohn’s disease (CD), has been presented at the Italian Group for the Study of IBD in Palermo, Italy. The study of 397 patients (174 UC and 223 CD) – the largest of its kind to date – demonstrated that those who were switched from Remicade® to biosimilar infliximab (RemsimaTM or InflectraTM; 93 patients) demonstrated similar efficacy to that seen in patients receiving a biosimilar who had previously been naïve to anti-TNFα (217 patients) and to those receiving a biosimilar who had previously been exposed to one or more biologics (87 patients) (response rate 95% vs 92% vs 91%, respectively). Safety was also found to be similar across the patient groups.

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ASIA-PACIFIC: First biosimilar guidelines in Hong Kong

Hong Kong has issued its first ever guidance on the evaluation and registration of biosimilar products, which came into effect on January 1, 2016. Although Hong Kong became part of China in 1997, it has retained independence with a number of its legal systems, including the regulation of pharmaceuticals. Issued by the Pharmacy and Poisons Board (PPB) of Hong Kong, the biosimilars guidance lays down two strict conditions that must be taken into account before submitting an application for product registration:

  1. The reference biologic product must have been registered in Hong Kong for more than 8 years.
  2. Only biosimilar products that have already been granted marketing authorization by a regulatory agency in at least one of these countries/regions – Australia, Canada, the EU, Japan, or the US – will be considered for registration as a biosimilar by the PPB.

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UNITED STATES: US Food and Drug Administration (FDA) approves Eli Lilly’s Basaglar as a “follow-on biologic” of insulin glargine

In January, the FDA approved Eli Lilly's diabetes drug BasaglarTM (insulin glargine) as a “follow-on biologic”. Lilly had in fact received tentative approval of Basaglar in August 2014, but the FDA declined to grant final approval at that time due to ongoing patent litigation between Lilly and Sanofi (makers of the originator Lantus®), which was eventually resolved in late 2015. Basaglar, which is approved for use in both type 1 and type 2 diabetes, is the first insulin product to be approved via the 505(b)(2) approval pathway. This means it is not strictly considered a biosimilar in the US because it was not approved via the 351(k) pathway, which was set up specifically for biosimilars. The 351(k) pathway requires candidate drugs to be compared with existing originator products approved under the Public Health Service Act, which governs the process. In this case 351(k) could not be used, because branded insulin glargine (Lantus) was approved under another law. Basaglar – which joins a few other follow-on biologics approved via the 505(b)(2) route – was approved as a biosimilar in Europe last year.

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UNITED STATES: Physician groups urge Congress to insist on unique biosimilar billing codes

Six medical groups representing a broad spectrum of biologic prescribers (the Alliance for Patient Access, American Association of Clinical Endocrinologists, American College of Rheumatology, American Gastroenterological Association, Biologics Prescribers Collaborative, and the Coalition of State Rheumatology Organizations) have sent a joint letter to Senator Orrin Hatch (Republican, Utah), urging Congress to direct the Centers for Medicare & Medicaid Services (CMS) to reverse its decision about biosimilar payment rates and codes. Despite strong concerns from many stakeholder groups, the CMS recently finalized the Medicare reimbursement of biosimilars policy, placing all biosimilar products under the same billing and payment code. Opponents who favor unique payment codes for each individual biosimilar fear that “the coding policy will interfere with the ability to track and trace each biosimilar medicine, which could have grave patient safety implications”.

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UNITED STATES: Outcome of second court case on biosimilar launch timing supports originator manufacturer

A Florida district court has granted Amgen (manufacturers of Neulasta®, originator pegfilgrastim) a preliminary injunction against Toronto-based Apotex, preventing it from launching its biosimilar of pegfilgrastim for 180 days once it gains FDA approval. The same ruling delayed Novartis from launching Zarxio (filgrastim-sndz), the first FDA-approved biosimilar, last year. Apotex had argued that, by complying in August last year with the requirements of the “patent dance” (i.e. providing details to Amgen of its candidate product’s application, manufacturing process, and the Neulasta patents that it might infringe), it was allowed to opt out of providing the 180-day notice of marketing. Amgen disagreed with Apotex’s right to opt out, which was why the case went to court. After the judge ruled that the 180-day notice provision is actually mandatory, the Generic Pharmaceutical Association’s Biosimilars Council spoke up, arguing that Congress never meant for the 180-day notice to add 6 months of exclusivity to biologics: “By its very definition, the 12-year exclusivity period should operate to prevent a biosimilar’s launch for only that length of time and no more”, the Council said.

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EUROPE: First etanercept biosimilar approved by European Medicines Agency (EMA)

Samsung Bioepis (the joint venture between Biogen and Samsung Biologics) has been granted EMA approval for Benepali®, their biosimilar of the anti-TNF biologic etanercept. Benepali is the first etanercept biosimilar to be licensed in Europe, and is indicated for the treatment of adults with moderate-to-severe rheumatoid arthritis (RA), psoriatic arthritis, non-radiographic axial spondyloarthritis, and plaque psoriasis. The 52-week, double-blind, Phase 3 clinical study included in the data package, randomized 596 patients with moderate-to-severe RA despite methotrexate therapy, across more than 70 sites in 10 countries to receive Benepali or the originator Enbrel® in a 1:1 ratio. Analysis of the primary endpoint demonstrated that Benepali had equivalent efficacy to Enbrel, as shown by the ACR20* response at Week 24, which was subsequently confirmed at Week 52. The safety and immunogenicity profile of Benepali was also similar to that of Enbrel throughout the study. Results from the RA study were considered sufficient for extrapolation of the license to the three other indications.

*American College of Rheumatology score indicating symptomatic improvement of at least 20%.

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EUROPE: New EU report highlights the impact and importance of biosimilar competition

A new report entitled “The Impact of Biosimilar Competition” has been published by IMS Health for the European Commission, with contributions from the European Federation of Pharmaceutical Industries and Associations (EFPIA), the European Biosimilars Group (EBG), and the European Association of Bioindustries (EuropaBio). Based on data from 2014, the report offers an independent source of information on which future evidence-based policy discussions may be based. Five key takeaways from the report are:

  • Sustainable competition can lead to both price decreases and increased access to treatment with high quality biologics earlier in the treatment algorithm.
  • Increased patient access is most pronounced in countries that originally had low usage of biologics.
  • There is a weak correlation between biosimilar market share and price reduction (and, as biosimilar medicines have a more sophisticated and costly development program compared with generic medicines, the same price reductions cannot be expected).
  • Uptake of biosimilar medicines varies widely between countries and across therapeutic areas.
  • Product portfolios are diversifying with manufacturers expanding into the biosimilar market, while also continuing to innovate to improve the standard of care.

IMS Report >
(Select Platform on Access to Medicines in Europe. Select Projects. Scroll down to Market Access for Biosimilars.)

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EUROPE: EMA plans update of biosimilar guidance for recombinant interferon alpha products

The EMA’s guidance on pre-clinical and clinical development of biosimilars of products containing recombinant interferon alpha (and pegylated recombinant interferon alpha) was published in April 2009. Although no products containing biosimilar interferon alpha have so far been licensed in the EU, the EMA is planning to update the guidance based on experience gained with license applications for originator products and recent scientific advice on biosimilar interferon alpha. A draft concept paper has been issued for public input and the first draft of the revised guideline is expected in Q2 this year.

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EUROPE: First biosimilar of teriparatide under review at EMA

Hamburg-based biotech company, Richter-Helm BioTec GmbH & Co. KG, has announced that the EMA has accepted its submission for a proposed biosimilar of Eli Lilly's Forteo® (teriparatide). Teriparatide is identical to the biologically active fragment of human parathyroid hormone, stimulating bone formation and increasing bone density. It is used in both men and women at high risk of osteoporosis-related fracture (often due to long-term use of steroids), those who have already sustained fractures related to osteoporosis, and those who cannot use other osteoporosis treatments.

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EUROPE: Belgian medical sector commits to increased use of biosimilars following government intervention

Belgium’s pharmaceutical and hospital networks have agreed to boost their use of biosimilars following intervention by the government as they currently lag very far behind other EU countries in this respect. Federal health minister Maggie De Block has signed an agreement with the medical sector and the pharmaceutical industry to encourage the use of biosimilars in Belgium, which is “necessary to keep healthcare affordable for both citizens and the government”. De Block fears that producers of biosimilars will lose interest in the Belgian market if the situation doesn’t change. A working group will monitor the use of three biosimilars and if there is no progress by July, legislative measures could be taken.

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LATIN AMERICA: Over a third of Latin American biologic prescribers are still unfamiliar with biosimilars, new survey shows

A 15-minute web-based survey in their native language was sent to a total of 6,650 prescribers in four countries in Latin America: Argentina, Brazil, Colombia, and Mexico. Responses obtained from a total of 399 (6%) of these physicians were translated into English for analysis and reporting purposes. Of those who said that they prescribed biologic medicines, 35% did not consider themselves familiar with biosimilars, and 30% were not aware that a biosimilar may be approved for all the indications of the innovator product on the basis of clinical trials in only one of those indications. Understanding of how biologics are identified when reporting adverse events was found to vary between countries. Respondents were split evenly between those who believed switching between biologics with the same non-proprietary name was safe and would achieve the same result, and those who did not.

Survey report >

January 2016   +

GLOBAL: Amgen files for adalimumab biosimilar approval in both the United States and Europe

Ahead of the escalating competition to be the first to apply for a biosimilar of adalimumab (Abbvie’s Humira®, the world's biggest-selling drug), Amgen has submitted its data package for its adalimumab biosimilar candidate ABP501 to both the US FDA and, shortly afterwards, to the EMA. Humira patents officially expire in the US in 2016 and in most EU countries in 2018. Nevertheless, Abbvie has so far remained confident that Humira’s complex and multi-layered patent protection arrangements will ensure it does not face biosimilar competition in any market until 2022. Whether this holds true remains to be seen. In the US, Amgen’s FDA submission signals the countdown to the complex exchange of intellectual property information known colloquially as the ‘patent dance’.

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GLOBAL: New publication compares current biosimilar naming conventions around the world

A new publication from researchers at the Tufts CSDD includes a summary of biosimilar naming policies from regulatory authorities around the world, as they currently stand. Key information is shown in the table below.


Biosimilar naming policy

World Health Organization

The WHO first introduced the concept of a biological qualifier (BQ) for naming biologics back in 2014. The WHO has issued a draft proposal, which suggests that the BQ (a code consisting of four random consonants) would be used in conjunction with the International Nonproprietary Name (INN), but not actually be part of it.

European Union
(European Medicines Agency)

In the EU, both the brand name and INN are used to identify the specific biologic product, whether it is an originator product or a biosimilar. The EMA has approved biosimilars with the same INN as their originator biologics for more than 6 years in a system that has proved effective. Biosimilars have been successfully tracked in the marketplace using their brand name and other identifiers, e.g. batch numbers, currently in place for product recognition. European regulators have reported 96.2% product identification across three product classes (filgrastim, epoetin, somatropin).

United States 
(Food and Drug Administration)

The US FDA has issued draft guidance on naming biosimilars. The agency is proposing that all biologics and biosimilars have the same INN, but that a unique 4-letter suffix – composed of four lower case letters – should be added to the names to distinguish them from one another.

(Pharmaceuticals and Medical Devices Agency)

Japan’s regulators require that biosimilars use the INN of the originator product, plus ‘biosimilar’ and a number indicating the order in which the biosimilar was approved in Japan (compared with other biosimilars of the same originator).

(Therapeutic Goods Administration

Australia’s drug regulatory agency had previously proposed that all biosimilars in Australia have distinguishable names, but is now reviewing its policy following recent international developments in the area of biosimilar naming.

South Africa
(Medicines Control Council)

The South African regulator’s naming policy simply requires that the holder of the certificate of registration ‘is responsible for ensuring that the product is traceable, i.e. reflection of the proprietary name of the product on the adverse event reports’.

Related article 1 >

Related article 2: Stergiopoulos S, Getz K. Evaluating AE reporting of two off-patent biologics to inform future biosimilar naming and reporting practices. Drug Saf (2015) 38:687–692.

EUROPE: First etanercept biosimilar receives positive opinion from EMA committee

The EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of Samsung Bioepis’ etanercept biosimilar Benepali® (previously known as SB4). If approved, Benepali will be the first biosimilar of Enbrel® granted approval in the EU, as well as the first subcutaneous anti-TNF biosimilar available in this market. Currently, South Korea is the only highly regulated market to have approved etanercept biosimilars. Samsung Bioepis had its etanercept biosimilar approved in Korea in September (where it is called Brenzys®). Meanwhile, in October, the US FDA accepted Sandoz’s application for approval of its etanercept biosimilar candidate (GP2015), which has not so far been submitted to the EMA.

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EUROPE: Spain urged to reverse biologic price control law to incentivize biosimilar competition

In contrast to other EU nations, Spain does not allow manufacturers of originator drugs for which patents have expired to charge any more for their products than the makers of rival biosimilars (the same law applies to small molecule brands and their generics). Now the European Generics and Biosimilar Medicines Association (EGA) and the Spanish Generic Medicines Association are lobbying the Spanish government to let originators in Spain charge their original price (pre-patent expiry) to incentivize biosimilar marketing and competition within Spain.

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EUROPE: Local payers within the UK’s NHS may be given incentives to switch to biosimilars

NHS spending in secondary care has risen by 15% over each of the last two financial years and the greatest rise in expenditure has been related to high-cost specialist drugs, which are nearly all biologics. Leading NHS decision-makers – who convened in London in November at the Ethical Medicines Industry Group (EMIG) conference – are considering giving local NHS budget-holders incentives to switch to biosimilars within their formularies in order to help reduce financial pressures on the UK’s health service. They are proposing that NHS payers across the UK could negotiate a 'year of care' tariff with biosimilar manufacturers at a price that provides savings against the originator product. The incentive for this course of action would be a so-called 'gain share opportunity', which allows local NHS payers to utilize their savings for other purposes.

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ASIA-PACIFIC: Indian biosimilar regulatory guidelines to be overhauled

The Indian health ministry has announced that it plans to revamp guidelines for approving biosimilar drugs to make the regulatory pathway more robust and bring it into alignment with rigorous international standards. The original Indian guidelines were released in 2012, but it is now acknowledged that they were not specific enough in certain areas, which caused issues with misinterpretation. Officials say the revised guidelines will be finalized after consultation with academic institutions, industry and other stakeholders, with the aim of ensuring that biosimilars developed within India are more likely to gain approval in highly regulated Western markets. 

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ASIA-PACIFIC: Biosimilar infliximab officially substitutable for the originator in Australia

In Australia, December 1st saw biosimilar infliximab (InflectraTM) officially added to the Pharmaceutical Benefits Scheme (PBS) that subsidizes prescribed medications for Australian citizens. The listing confirms that Inflectra will be substitutable for the originator Remicade® at the pharmacy level, without prescriber notification, although patients will be advised of the switch. Comprehensive prescriber and patient factsheets explaining the Inflectra PBS listing have been posted on the PBS website.

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UNITED STATES: First application for pegfilgrastim biosimilar is accepted for FDA review

The FDA has received an application from Sandoz for a biosimilar of pegfilgrastim (Neulasta®), a long-acting form of the recombinant human granulocyte colony-stimulating factor (G-CSF) analogue filgrastim. So far, no pegfilgrastim biosimilar applications have yet been filed in Europe or other highly regulated markets. The opportunity for FDA approval has arisen because the US patent on Neulasta expires before Europe’s. The Sandoz biosimilar now joins the FDA approval queue alongside candidate biosimilars of infliximab, etanercept, filgrastim, and epoetin alfa.

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December 2015   +

GLOBAL: Adalimumab biosimilar candidates mount up but originator patents could keep them at bay

Amgen's adalimumab biosimilar has demonstrated comparability to AbbVie’s originator Humira (the world’s top selling drug) in a Phase 3 rheumatoid arthritis trial and now joins many other contenders, including candidates from Merck/Samsung Bioepsis, Novartis, and Baxalta/Momenta.  However, AbbVie’s CEO says many of Humira’s numerous patents could protect the product from biosimilar competitors until at least 2022. Although the composition patent for Humira expires in 2016, the later patents covering the formulation and method of manufacture of the drug, and those related to the product delivery device, could stave off biosimilar competitors for at least the following 6 years.  In addition, AbbVie may well decide to sue the makers of adalimumab biosimilars to delay their arrival. Legal experts believe that a patent defense lawsuit launched by AbbVie, even if it loses, could go on until 2019.  

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GLOBAL: Celltrion submits their biosimilar rituximab candidate to European regulators

After Boehringer Ingelheim terminated the development of BI 695500, its proposed rituximab biosimilar, in October 2015, many believed that Sandoz would be the first to submit its rituximab biosimilar candidate, GP2013, in highly regulated markets. However, it has emerged that Korean biotech company Celltrion submitted an application for CT-P10, its proposed rituximab biosimilar, to the European Medicines Agency (EMA) on 10 November 2015. Key questions remain, however. Reports in Korean media have only sought to confirm the submission of CT-P10 to the EMA, but have stopped short of providing any information about which indications Celltrion is seeking. There is also no mention of which data were included in the submission.

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GLOBAL: Another etanercept biosimilar clears Phase 3 trials

Coherus BioSciences Inc. and Baxalta Inc. have announced that their etanercept biosimilar candidate met its primary endpoints in a Phase 3 trial versus the originator Enbrel, in patients with moderate-to-severe chronic plaque psoriasis. We reported last month on Samsung Bioepis’ candidate etanercept biosimilar Brenzys®, which had shown comparability to Enbrel® in rheumatoid arthritis. So far, the only highly regulated market in which etanercept biosimilars have been approved is South Korea.

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UNITED STATES: FDA rejects Hospira’s EPO biosimilar – but re-application is intended soon

Hospira’s application for a biosimilar version of Amgen’s Epogen (EPO) has been rejected by the US Food and Drug Administration (FDA). Although the details of the FDA’s decision are not public, Hospira has stated that it has additional evidence to put forward without needing to conduct new trials and intends to resubmit its application to the FDA in the first half of 2016. The FDA’s rejection of Hospira’s product suggests that the approval of Zarxio may ultimately provide little guidance for more complex products. In addition, although Hospira’s EPO biosimilar (trade name Retacrit) has been approved in Europe since 2007, significant marketing history outside the US clearly does not guarantee FDA approval. Given the complexity of many biosimilars, it seems unlikely that the floodgates are about to open for these products in the US.

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UNITED STATES: Dedicated post-marketing surveillance program for biologics and biosimilars is on its way

The Academy of Managed Care Pharmacy (AMCP) have announced a major milestone in the formation of the Biologics & Biosimilars Collective Intelligence Consortium (BBCIC) – a public service initiative that will draw on large sets of de-identified pharmacy and medical data to provide unbiased scientific information on the safety and effectiveness of marketed biosimilars and their corresponding novel biologics. The BBCIC has secured financial support from multiple healthcare stakeholders for this effort and will launch research activities in January 2016. The BBCIC is the only research network dedicated to monitoring biosimilars and will apply the same scientific, analytic methods used by the FDA Sentinel initiative, a post-market surveillance system that tracks the safety of pharmaceuticals once they reach the market.

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UNITED STATES: CMS sticks to proposed biosimilars reimbursement policy

Campaigners for biosimilars have failed to convince the Centers for Medicare and Medicaid Services (CMS) to revise a reimbursement policy that they fear will discourage biosimilar prescribing. In late October 2015, CMS finalized its decision to assign one payment calculation and billing code for biosimilars covered by Medicare Part B, while retaining a different code for the originator product. Opponents fear that lumping all biosimilar products into a single payment calculation, separate from the reference product, will curb the use and development of these less-costly therapies.

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UNITED STATES: Federal Circuit denies petitions to rehear biosimilar patent dance decision

The Federal Circuit has declined to review the decisions it made in the Amgen vs Sandoz lawsuit that followed the US Food and Drug Administration (FDA) approval of the first US biosimilar Zarxio earlier this year. In the portion of the decision Amgen disagreed with, the panel held that a biosimilar applicant does not have to share its FDA application with the originator product manufacturer or follow the patent dispute resolution procedures set forth in the Biologics Price Competition and Innovation Act (BPCIA). In the portion of the decision Sandoz disagreed with, the panel held that a biosimilar applicant must give 180 days’ pre-marketing notice to the originator manufacturer and cannot do so until after the FDA has approved the biosimilar product.

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EUROPE: Merck lowers price of Remicade in UK by approximately 25%

Earlier this year, the UK’s National Institute for Health and Care Excellence (NICE) approved two biosimilar versions of Remicade (infliximab). Because of the competitive pricing pressure this has placed on branded Remicade (a 25% decline in sales during the second quarter of this year), Merck has agreed to lower its price in the UK by around 25%, offering a discount of £48 million (US$73.3 million) based on £191 million (US$292 million) in Remicade sales.  According to Merck, Remicade is now priced to compete effectively in the UK with the biosimilar infliximab products, Inflectra and Remsima – although a Napp spokesperson has stated that Remsima is being offered to the National Health Service (NHS) at discounts of up to 50% of the original list price of Remicade, depending on the deal agreed with each tendering region within the UK.

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ASIA PACIFIC: India falling behind on biosimilar R&D

Although India has dominated the generic drugs industry for decades, new reports indicate it is falling behind in the race to make biosimilars. Although Indian firms have launched various copies of biologic drugs on the domestic market, where regulatory barriers are relatively low, they are being overtaken by European, American, and South Korean firms in the race to supply lucrative Western markets, which are highly regulated. Only three Indian groups – Biocon Ltd, Dr Reddy's Laboratories Ltd, and Intas Pharmaceuticals Ltd – are working with partners on biosimilars aimed at the US and Europe.

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ASIA PACIFIC: Roche secures temporary court injunction on trastuzumab biosimilar in India

Roche has won a temporary injunction from the Delhi High Court to block the expected launch of a trastuzumab biosimilar in India by Reliance Life Sciences. Roche argued that Reliance’s product approval was based on submission of Phase 3 study results alone, with no Phase 1 or 2 data submitted. They stated that this invalidates the submission and that they had concerns about the quality and safety of the candidate product. Meanwhile, Mylan and Biocon are continuing their battle with Roche in the Delhi High Court over a launch last year of their trastuzumab biosimilar. A judgment is possible by the end of the year.

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ASIA PACIFIC: Malaysian consumer group urges government not to sign the TPP deal

The Consumers Association of Penang (CAP) has expressed outrage that the Malaysian government “has negotiated an agreement that will greatly impact the lives of all Malaysians in secret, for so long. Of particular concern is the new obligation for Malaysia to provide 5 years of market exclusivity for biologics medicines even if there is no patent, thus preventing cheaper biosimilars from entering the market”. The CAP is now urging the government: “don’t sign the TPP – the deal that will rob our future”.

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LATIN AMERICA: New post-marketing study in Mexico shows effective pharmacovigilance is possible locally

Mexican regulations call for a stringent pharmacovigilance program for biologics, including biosimilars (known locally as biocomparables). However, the issue of traceability has not yet been fully resolved. In the Mexican social security system, medicinal products are identified by codes, with originator biologics and biocomparables receiving the same code. To overcome this issue, a prospective, non-interventional, pharmacovigilance study of different filgrastim products provided at the National Cancer Institute of Mexico was carried out. The study included giving diaries to 373 patients to record adverse drug reactions (ADRs), as well as examination of clinical histories. In 93% of the cases, it was possible to trace the drug name, expiration date, brand name, and batch number of the dispensed products. All recorded ADRs had been reported previously. The authors concluded that their approach allowed good quality ADR and traceability information on filgrastim use to be obtained in Mexico.

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November 2015   +

GLOBAL: Trade Pacific Partnership (TPP) discussions conclude: US steps down on 12-year exclusivity for biologics

The TPP (the largest free trade agreement in history) concluded its discussions in Atlanta (GA, US) on 5 October 2015 with a tense stand-off between the US and Australia over patent protection for innovator biologics. The Office of the United States Trade Representative (USTR) had proposed a 12-year period of exclusivity for biologics for its Pacific Rim partners, in line with current US healthcare reform legislation. In the end, the US has bowed to pressure mainly from Australian trade minister Andrew Robb and met his demand for a mandatory minimum of 5 years of exclusivity.  However, because regulatory requirements for post-marketing pharmacovigilance data will be required, the total exclusivity period may approach 8 years. Although the shorter exclusivity period secured by Australian negotiators is good news for patient access to more affordable biologic therapies, Médecins Sans Frontières (Doctors without Borders) has pointed out that several of the countries involved in the TPP previously had no, or very limited, exclusivity periods for innovator biologics but now have to enforce the 5‒8 year minimum. In addition, the TPP agreement will not impact the data protection period of the US itself, which currently remains at 12 years. Over the next several weeks, the agreement will undergo what is referred to as the “legal scrub”, involving scrutiny of the details by lawyers in each participating nation. The agreement is expected to take effect in early 2016.

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GLOBAL: Biosimilars make their mark on international industry association

The International Generic Pharmaceutical Alliance (IGPA) – launched in 1997 – has changed its name to the International Generic and Biosimilar Medicines Association (IGBA). In doing so, the IGBA has become the first global trade association encompassing biosimilar medicines in its name as well as within its agenda. The common IGBA principles are: access to affordable quality medicines, ensuring timely access for patients, global harmonization of regulations related to quality, improving regulatory and legal expertise, and preventing the production and trade of counterfeit versions of medicines.

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GLOBAL: Positive results in Phase 3 bevacizumab biosimilar trial

Amgen and Allergan’s bevacizumab biosimilar candidate ABP 215 has shown clinical comparability (in terms of efficacy, safety, and immunogenicity) to the originator Avastin® in a Phase 3 trial in non-small cell lung cancer (NSCLC).  Patents for Avastin are set to expire in 2022 in Europe, and in 2019 in the United States. There are estimated to be around 15 biosimilars of bevacizumab currently in development. Amgen/Allergan plan to be ready with their bevacizumab biosimilar well in advance of patent expiration, positioning them to be first to market in highly regulated countries.

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GLOBAL: Positive results in Phase 3 etanercept biosimilar trial in rheumatoid arthritis

A 24-week trial (n=596) has demonstrated the clinical comparability of Samsung Bioepis’ candidate etanercept biosimilar Brenzys® with the originator Enbrel® in patients with rheumatoid arthritis. So far the only highly regulated market in which etanercept biosimilars have been approved is South Korea. Brenzys® is under review at the European Medicines Agency (EMA). Meanwhile, in early October, the US Food and Drug Administration (FDA) accepted its first 351(k) application for an etanercept biosimilar (in this case from Sandoz).

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EUROPE: British healthcare stakeholders present collaborative biosimilars publication aimed at patients

“What is a biosimilar medicine?” is a new publication developed through a collaboration between NHS England, the Medicines and Healthcare products Regulatory Agency (MHRA), the National Institute for Health and Care Excellence (NICE), the Royal Pharmaceutical Society (RPS), and three pharmaceutical industry trade associations (the Association of the British Pharmaceutical Industry [ABPI], the UK BioIndustry Association [BIA] and the British Generic Manufacturers Association [BGMA]). This document is the first collaborative publication on biosimilar medicines at a country level, following the 2013 launch of the European Commission’s consensus document, “What you need to know about biosimilar medicinal products”.

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EUROPE: National Health Service (NHS) England rules out automatic substitution of biosimilars by pharmacists

In its latest guidance, NHS England has confirmed that English pharmacists are not free to dispense biosimilars in place of originators. The rules ban automatic substitution of biosimilars without consent from the prescribing physician. NHS England also requires doctors to prescribe biologics by brand name, rather than by international nonproprietary name (INN). The rule will change the way British doctors traditionally write their prescriptions, which has always been by INN. However, in the UK, biosimilars use the same INN as originators, so brand-name prescribing will be needed to prevent confusion and accidental product substitution.

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EUROPE: UK patient pressure group seeks compulsory licensing for Kadcyla biosimilar to treat breast cancer

Roche’s breast cancer drug Kadcyla (trastuzumab emtansine) was rejected for NHS funding by the National Institute for Health and Care Excellence (NICE) last year and subsequently rejected by the “last resort” Cancer Drugs Fund. Now, an outspoken patient pressure group is calling on Britain's health minister to take a radical step: override Kadcyla’s patent and open the door for lower-priced biosimilars. Compulsory licensing is allowed under British law in special circumstances, as it is in many countries, but the maneuver is uncommon even in the cash-strapped developing world. A decision of this nature would be highly political.

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EUROPE: Turkish scientists aim to produce biosimilars for domestic market

Turkey’s top science body aims to produce biosimilar versions of cancer biologics for its domestic market – a rare example of a manufacturing initiative by a group that is not a commercial pharmaceutical or biotech company. The Marmara Research Center (MAM), working under the Scientific and Technological Research Council of Turkey (TÜBİTAK), has launched a project aiming to produce biosimilar drugs for Turkish cancer patients in view of Turkey’s current dependence on expensive foreign imports of biologic drugs.

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EUROPE: Five biosimilar applications under review by the EMA

According to the recently released list of applications for new human medicines under evaluation by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), the agency is currently reviewing five biosimilar applications: one for human insulin, one for infliximab, two for the blood-clot buster enoxaparin sodium, and one for the arthritis treatment etanercept, for which there are currently no biosimilars available on the European market.

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UNITED STATES: US physicians need more detailed education on biosimilars

A white paper released by QuantiaMD (a leading online social community for US physicians) has identified a lack of awareness and education among both primary care physicians and specialists about emerging biosimilars. The report “Reading the Signs: A Roadmap for Engaging Physicians in the Biosimilars Discussion”, found that while physicians recognize the cost advantage that biosimilars would bring to the healthcare industry, they lack detailed information on these products that would give them the confidence to translate their awareness into action.

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UNITED STATES: Senators urge FDA to finalize biosimilar guidance on interchangeability and labeling

Members of a Senate Health, Education, Labor, and Pensions (HELP) subcommittee have urged the US Food and Drug Administration (FDA) to crystallize its biosimilar rules to avoid the kind of challenges generic drugs faced when introduced to the market three decades ago. Speaking before the subcommittee, Dr Janet Woodcock, Director of the FDA's Center for Drug Evaluation and Research, said the agency was “on track” to issue guidance on the interchangeability and labeling of biosimilars by the end of the year. But Senator Elizabeth Warren (D-Mass.) countered that the FDA has had 5 years since biosimilars received a pathway for FDA approval in 2010. She said any further delay could hinder the potential for biosimilars to provide savings on drugs prices. “It is time now to get this done. The longer it takes you to set the rules, the longer patients will be stuck with paying only one very expensive option to treat their medical needs” she insisted.

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UNITED STATES: Patient advocacy groups consulted on FDA decision-making

The Senate Committee on Health, Education, Labor, and Pensions (HELP) has held a hearing on the US Food and Drug Administration’s (FDA) system for approving biosimilars, to which it invited an organization called Patients for Biologics Safety & Access (PBSA). PBSA is a coalition made up of more than 20 patient advocacy organizations and is dedicated to ensuring the patient voice is heard by the FDA as it works through the biosimilar approval process.

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UNITED STATES: Could biosimilar naming guidance have left FDA trapped?

Eagerly awaited interchangeability guidance will be at odds with the FDA’s recent guidance on naming biologic products with a 4-letter suffix, according to a panel of biosimilars experts. The panel point out that when interchangeability guidelines come along, the use of a differentiator, like this unique suffix, defeats the purpose of a product being seen as fully interchangeable.

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CANADA: Health Canada criticized for being overly restrictive with biosimilars

Health Canada's regulatory approach to biosimilars (or SEBs as they are locally known) has been overly restrictive, according to industry insiders at the recent International Generic and Biosimilar Medicines Association (IGBA) conference in Toronto. The key example discussed was Health Canada's approach to the biosimilar drug Inflectra (an infliximab biosimilar), which differed markedly from that of Europe. Health Canada approved Inflectra for rheumatoid arthritis but not for inflammatory bowel disease (IBD), saying that the data in that indication were not convincing. However, spokespeople for the European Medicines Agency (EMA) insisted that the specific IBD data Health Canada took exception to were "not clinically relevant".  According to the EMA, the majority of prescriptions for Inflectra in 26 European countries are for IBD.

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ASIA-PACIFIC: Australian government to invest heavily in biosimilar awareness projects

The Australian government is investing AU$20 million over 2015‒2018 for activities designed to improve awareness and confidence in biosimilar medicines, for both health professionals and consumers.  

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ASIA-PACIFIC: Australian Pharmaceutical Society highlights patient safety as top priority

In the wake of the Australian government’s controversial decision to allow automatic pharmacist substitution of biosimilars, the Pharmaceutical Society of Australia (PSA) has released a Biosimilar Medicines Position Statement, in which it says patient safety is a prime concern. The statement asserts that risk assessment in relation to biosimilars should not only include evaluation of safety and efficacy by the Australian regulatory authority, but also consideration by the Pharmaceutical Benefits Advisory Committee (which recommends the listing of new medicines on the Pharmaceutical Benefits Scheme), and clinical assessment by individual prescribers. National President of the PSA, Joe Demarte, said pharmacists should follow substitution principles that respect the choice of prescribers and patients, rather than making automatic substitution of biosimilars for originators.

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LATIN AMERICA: Brazil emerges as attractive partner for global biosimilar developers

An emerging biosimilars company in Taiwan has hosted a major delegation of Brazilian government officials and top-ranking biotech executives, who visited the company's headquarters in support of a partnership to produce affordable, world-class biosimilars. Brazil has become an increasingly attractive target for biosimilar developers in many parts of the world because the Brazilian government strongly supports its domestic manufacturers in working with international partners.

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MIDDLE EAST: Jordan issues formal biosimilar regulatory guidelines

The regulatory authority in Jordan has issued its formal guidelines for biosimilar development and approval. The guidelines are closely based on those of the European Medicines Agency (EMA). The EMA principles have been in use within draft guidelines in Jordan since 2008.

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AFRICA: South African official to take up chair of newly re-named IGBA

As of 1 October 2015, the chairmanship of the newly re-named International Generic and Biosimilar Medicines Association (IGBA) passes to Vivian Frittelli, Chief Executive Officer of South Africa’s National Association of Pharmaceutical Manufacturers (NAPM), which represents the generic and biosimilar medicines industries in South Africa. “In an era when increasing demands are being made on the world’s healthcare services, generic and biosimilar medicines provide a major benefit to society by ensuring patient access to quality, safe and effective medicines while reducing the cost of pharmaceutical care”, Mr Frittelli commented.                   

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October 2015   +

GLOBAL: International evidence supports clinical efficacy and safety of Zarzio in routine clinical practice

In routine clinical practice, the clinical efficacy and safety of Zarzio,* a biosimilar version of filgrastim, are similar to that of the originator filgrastim (Neupogen) for the prevention of chemotherapy-induced (febrile) neutropenia, according to a new real-world study published online ahead of print in the journal Supportive Care in Cancer. In the international, prospective, observational, open-label MONITOR-GCSF study, researchers enrolled 1447 cancer patients treated with myelosuppressive chemotherapy who were receiving prophylaxis with biosimilar filgrastim. The new study adds to consistently accumulating evidence for the comparable clinical benefits of Zarzio compared to Neupogen.

*Zarzio is the European spelling of the product; the US spelling is Zarxio.

Reference: Gascon P et al. Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study). Supportive Care in Cancer 2015 Aug 27. [Epub ahead of print].

ASIA-PACIFIC: Australia approves Inflectra, an infliximab biosimilar, and deems it substitutable by pharmacists

Inflectra, a biosimilar of infliximab, has been licensed in Australia for eight inflammatory conditions: rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis (AS), adult and pediatric Crohn’s disease, adult and pediatric ulcerative colitis, and plaque psoriasis.  The approval was based on the results of pivotal trials in patients with RA and AS, which demonstrated therapeutic comparability to the originator Remicade and justified extrapolation to the other indications in the opinion of the Australian regulatory authority.  Inflectra – Australia’s first biosimilar monoclonal antibody – has also been controversially ‘a’ flagged by the Pharmaceutical Benefits Advisory Committee (PBAC), which means Australia is the world’s first highly regulated market to allow pharmacy-level substitution of a monoclonal antibody biosimilar for an originator.  On 8 September 2015, five Australian professional and patient associations wrote a joint letter to Health Minister Sussan Ley expressing concern about the ‘a’ flagging decision.

Related articles  1>  2>

ASIA-PACIFIC: South Korea plans product-specific guidelines for insulin biosimilars

As more biosimilar products are set to be launched in South Korea, with a high number of ongoing late-stage clinical trials, the country is seeking to introduce a separate guideline for insulin biosimilars, much as the EMA has done. While South Korea introduced its formal biosimilar guidelines relatively early, a local institute (the Korea Economic Research Institute) has suggested that these still need to be improved, pointing to a lack of clarity and implementation issues which may curb the global competitiveness of the domestic biosimilar industry. The proactivity of the South Korean regulators, together with the country’s strong biosimilars pipeline, is helping to reinforce South Korea’s leading role in the biosimilars field in Asia.

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UNITED STATES: First FDA-approved biosimilar launched on 3 September 2015

Sandoz’ Zarxio, the first biosimilar approved by the FDA, is finally on the market in the US. The product was launched on 3 September after a 6-month delay caused by a patent infringement lawsuit initiated by Amgen, manufacturer of the originator filgrastim Neupogen. Zarxio (which has the non-proprietary name filgrastim-sndz) is being marketed at a wholesale price 15% lower than that of Neupogen. For Medicare, this amounts to a relatively small saving but biosimilar discounts typically evolve over time and the price of Zarxio may decrease later, as seen in the EU, where it is currently 20‒30% cheaper than Neupogen.

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UNITED STATES: FDA releases long-awaited proposal for biosimilar naming – which potentially conflicts with WHO

The FDA has issued its much anticipated provisional naming guidance for biosimilars, which proposes that originator biologics and biosimilars are given the same non-proprietary name, but with a unique 4-letter suffix for all biologics, including originators. The proposed naming convention seeks to prevent inadvertent substitution of biological products that are not deemed interchangeable by the FDA and to support safety monitoring by making it easier to accurately track product usage. However the FDA’s proposal could create a situation the WHO wants to avoid: products with different names in different countries. The problem appears to stem from a fundamental difference in the two agencies’ philosophies for adding the 4-letter suffix (known as the biological qualifier). The FDA believes the suffix needs to be part of the non-proprietary name, while the WHO sees it as a separate identifier. The FDA is still seeking views on how to name biosimilar products deemed interchangeable with originators.

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UNITED STATES: First FDA-approved biosimilar launched on 3 September 2015

Sandoz’ Zarxio, the first biosimilar approved by the FDA, is finally on the market in the US. The product was launched on 3 September after a 6-month delay caused by a patent infringement lawsuit initiated by Amgen, manufacturer of the originator filgrastim Neupogen. Zarxio (which has the non-proprietary name filgrastim-sndz) is being marketed at a wholesale price 15% lower than that of Neupogen. For Medicare, this amounts to a relatively small saving but biosimilar discounts typically evolve over time and the price of Zarxio may decrease later, as seen in the EU, where it is currently 20‒30% cheaper than Neupogen.

Related articles: 1>  2>

UNITED STATES: FDA releases long-awaited proposal for biosimilar naming – which potentially conflicts with WHO

The FDA has issued its much anticipated provisional naming guidance for biosimilars, which proposes that originator biologics and biosimilars are given the same non-proprietary name, but with a unique 4-letter suffix for all biologics, including originators. The proposed naming convention seeks to prevent inadvertent substitution of biological products that are not deemed interchangeable by the FDA and to support safety monitoring by making it easier to accurately track product usage. However the FDA’s proposal could create a situation the WHO wants to avoid: products with different names in different countries. The problem appears to stem from a fundamental difference in the two agencies’ philosophies for adding the 4-letter suffix (known as the biological qualifier). The FDA believes the suffix needs to be part of the non-proprietary name, while the WHO sees it as a separate identifier. The FDA is still seeking views on how to name biosimilar products deemed interchangeable with originators.

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UNITED STATES: AbbVie wins 9th US indication for adalimumab (Humira) to lessen impact of looming patent expiry

AbbVie has been pre-emptive about Humira’s looming patent expiry and the potential loss of sales. A new indication approval in the US for the treatment of moderate-to-severe hidradenitis suppurativa (HS), a chronic inflammatory skin condition, is the latest development. Earlier this year, AbbVie secured European approval for Humira against HS, as well as developing a new formulation for the product, which causes less injection-site pain. The company now plans to file the drug in the US and EU for inflammatory eye diseases. However, despite the additional indications, biosimilar versions of adalimumab can still be developed for existing Humira indications soon to lose their patent.

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EUROPE: Substantial savings predicted from uptake of Remsima (infliximab biosimilar) in five EU countries 

Published online ahead of print in the journal Advances in Therapy, a new budget impact model has predicted significant annual cost savings resulting from the introduction of the infliximab biosimilar Remsima for inflammatory autoimmune diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, and psoriatic arthritis). The publication suggests that savings may range from €2.89 million (Belgium, 10% discount) to €33.80 million (Germany, 30% discount) per year. If any such savings were used to treat additional patients with Remsima, 250 (Belgium, 10% discount) to 2602 (Germany, 30% discount) additional patients could be treated.

Reference: Jha A et al. The budget impact of biosimilar infliximab (Remsima®) for the treatment of autoimmune diseases in five European countries. Adv Ther. 2015; 32(8):742‒56

EUROPE: Rheumatologists in five EU countries predict at least 30% of new RA patients eligible for biologics will receive biosimilars

Rheumatologists surveyed across the EU5 (France, Germany, Italy, Spain, and the UK) estimate that within the first year of biosimilar availability, more than 30% of RA patients newly starting on a biologic drug will receive the biosimilar version. Interviewed payers in most EU5 countries indicate that measures will likely be implemented to recommend or require the use of biosimilars, especially in patients first prescribed biologic therapy. Switching of branded agents to biosimilar counterparts is not likely to be mandated until rheumatologists and payers gain more experience with biosimilars, and long-term efficacy and safety data become available.

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EUROPE: Insulin glargine biosimilar launched in UK at 15% discount

The insulin glargine biosimilar Abasaglar (co-marketed by Eli Lilly and Boehringer Ingelheim) has arrived on the UK market priced at 15% less than the originator Lantus. Abasaglar was approved in Europe last September and introduced in some Eastern Europe markets earlier this year – including the Czech Republic, Slovakia, and Estonia where pricing has also been set at around a 15‒20% discount to Lantus. However, the UK launch of Abasaglar marks the first competition to Lantus in a major EU pharma market.

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September 2015   +

GLOBAL: Manufacturers of originator biologics are developing new tactics to fight competition

With biosimilars on the way, the manufacturers of top-selling originators are finding ways to enhance the competitiveness of their products beyond price cutting. Abbvie, makers of the world’s leading biologic Humira (adalimumab), recently received European Medicines Agency (EMA) approval for a new formulation specifically designed to reduce injection pain, injection volume, and potentially the number of injections required. The formulation is currently under review by the US Food and Drug Administration (FDA). Media reports suggest that part of the commercial strategy for the new formulation could be to encourage switching of patients to the new formulation of Humira before a biosimilar version of the drug is released in the US market. In the case of Neulasta (pegfilgrastim), manufacturer Amgen has developed a system that allows patients to receive treatment at home, rather than in a doctor’s office. Roche has been particularly active in enhancing the efficacy of its monoclonal antibodies for HER2-positive breast cancer (Herceptin) and chronic lymphocytic leukemia (Rituxan) by developing second-generation products (Perjeta, Kadcyla and Gazyva) that have outperformed these older biologics in head-to-head studies. Commentators have observed that these activities may well ‘raise the bar’ for biosimilar developers.

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UNITED STATES: Complex US patent situation continues to fuel legal disputes

Hot on the heels of its patent dispute with Sandoz – over the launch of the first FDA-approved biosimilar Zarxio – Amgen has now filed a lawsuit against Apotex, who are applying for FDA approval of a biosimilar version of Amgen’s Neulasta (pegfilgrastim). This is the first lawsuit in which the parties at least initially engaged in the intricate and carefully orchestrated set of information exchanges informally known as the ‘patent dance.’ But Amgen maintains that Apotex infringed patent law by providing notification of commercial marketing prior to FDA approval of its Section 351(k) application. Federal Circuit judges have already ruled in the case of Zarxio that, while information exchange is not mandatory, notification of commercial marketing must come after FDA approval. 

However, the case against Apotex is not altogether straightforward. In the Amgen v. Sandoz decision, the Court hinted that the Notice of Commercial Marketing may not be compulsory in instances where the biosimilar applicant has chosen to participate in the patent dance, which seems to be the case here. There appear to be numerous and complex reasons (both legal and commercial) why a biosimilar applicant may or may not decide to ‘dance’ and the progress of this second Amgen lawsuit is being closely watched by others to gain valuable insights into strategic decision-making. Meanwhile the absence of notice of an FDA advisory committee meeting to review the Apotex biosimilar application suggests that approval may not be imminent. 

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UNITED STATES: New US gastroenterologist survey reveals growing prescriber receptivity to biosimilars

The American Gastroenterological Association (AGA), the leading voice of the US gastrointestinal community, released the findings of a national survey of 180 gastroenterologists on biosimilars. The survey revealed that almost three-quarters of respondents were likely to prescribe biosimilars once they become available. Almost all respondents currently prescribe biologics to their patients, and most have, at some point, had to switch a treatment because of their patients’ insurance plans. James Lewis MD, Professor of Medicine at the University of Pennsylvania, commented: “Our members welcome access to new therapies like biosimilars, particularly if they can lower costs to patients without compromising the effectiveness and safety of our therapies.”

Notable findings of the survey include:

  • 72% of respondents report that they would be likely to prescribe biosimilars if they became available in the US, with 49% “extremely” or “very” likely to prescribe
  • 80% of respondents say they would place strong emphasis on the proven level of clinical similarity between a biosimilar and its originator biologic
  • 67% of respondents favored a policy whereby the FDA would not allow indication extrapolation in the approval of biosimilars for inflammatory bowel diseases
  • 55% of respondents believe that pharmacy-level substitution of interchangeable biosimilars should only be allowed with prescriber notification and 35% believe that pharmacy-level substitution should never be allowed.

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UNITED STATES: Sixteen US states now have legislation governing biosimilar substitution

As previously reported, many US states have begun to actively regulate the substitution of interchangeable biosimilars before any FDA-approved biosimilar has even hit the market. State biosimilar legislation passed to date has focused on the circumstances under which biosimilar substitution is permitted, notice requirements, and record retention time periods. As of July 1, 2015, 16 states have enacted legislation or set out administrative rules governing biosimilar substitution by pharmacists. A further four states currently have pending legislation that could pass before the end of the current legislative session. Key state requirements are as follows:

  • 14 of the 16 state laws require the pharmacist to notify the prescriber of the substitution. However, in one of these states, Virginia, the statutory provision requiring prescriber notification expired on July 1 this year and in another, Oregon, it is due to expire on January 1, 2016. The issue may well re-emerge as interchangeable biosimilars come closer to entering the market
  • 10 state laws require the pharmacist to notify the patient of the biosimilar substitution
  • Three state laws require the pharmacist to obtain the patient’s consent prior to dispensing a biosimilar as a substitute for the prescribed biological product
  • 10 state laws require that pharmacies maintain written records of biosimilar substitution for a set period of time, typically 2 years
  • Three states require the pharmacist to substitute the biosimilar product unless certain criteria are met. For example, in Tennessee, the prescriber must satisfy fairly strict standards to demonstrate that the prescribed biological product is medically necessary for the patient in question in order to prevent biosimilar substitution.

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UNITED STATES: Biosimilars Council warns Obama administration that the Trans-Pacific Partnership (TPP) looks set to seriously undermine access to biosimilars

The Biosimilars Council has written an open letter to President Obama warning that provisions in the Trans-Pacific Partnership (TPP) contradict the goals originally outlined in the Biologics Price Competition and Innovation (BPCI) Act of 2009 and will undermine consumer access to more affordable biologic medications. The TPP is a proposed trade agreement between the US and several Pacific Rim countries (Australia, Brunei Darussalam, Canada, Chile, Japan, Malaysia, Mexico, New Zealand, Peru, Singapore, and Vietnam). Its aims are to enhance trade and investment among the TPP partner countries in order to promote innovation, economic growth, and development. While TPP negotiations are not yet finalized, its current position on patent protection for originator pharmaceuticals appears to be at odds with the aims of the BPCI Act (a key part of the Patient Protection and Affordable Care Act).

The Obama administration has been aiming to reduce the US patent protection period for originator biologics from 12 years to 7 years in the interests of encouraging biosimilar competition and making biologic medicines more affordable for the US population, but it’s become clear that the US governmental team leading the TPP negotiations may prevent this by enforcing a 12-year period of patent protection within all TPP partner nations. And it seems there is more to this issue than just patent protection. A leaked draft of the TPP negotiations indicates proposals to extend data protection for originator clinical trial results, without which biosimilar developers cannot file their own applications. Médecins Sans Frontières (Doctors Without Borders) – a strong critic of the TPP – has raised the point that data protection agreements can prevent competitor drugs from launching even if the patent of the originator product has expired. 

Some media reports suggest that, in view of the significant opposition to these TPP proposals from many stakeholders, the US Trade Representative Michael Froman may agree to back down on some of them following a recent round of talks in Hawaii which failed to reach resolution. However, because all TPP negotiations have so far been conducted in secret, it is difficult to distinguish genuine developments from rumors.

See also ASIA-PACIFIC section

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LATIN AMERICA: Colombian regulatory standards for biosimilars under scrutiny

Members from 10 Colombian patient organizations have joined forces with the Global Alliance for Patient Access in querying what they consider to be a poorly defined “alternative approach” by the Colombian regulatory authorities to approving biosimilar medicines. The Colombian regulatory guidelines, which were issued in draft form in 2013, have not yet been finalized. However, stakeholders are concerned that although the draft guidelines declare that the required data must show the quality, efficacy and safety of a biosimilar, there are no specifications as to how these properties should be demonstrated by the applicant. There is also concern that the guidelines establish three possible routes to approval, including an abbreviated pathway, and that applicants may be unclear which route is most appropriate for their product. In a letter to the Colombian Ministry of Health and Social Protection, the patient groups emphasize the complexity of biological medicines and the potential impact of unwanted immunogenicity. Approving biosimilar medicines through anything other than a rigorous, data-driven process would be “highly troubling,” the signatories contend. They assert that, for Colombia’s physicians and patients to have confidence in biosimilar medicines, they must be assured that these therapies were approved via a process that meets the highest of standards, as lack of confidence in the approval process will undermine the very goal of ensuring access to biosimilar medicines.

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ASIA-PACIFIC: Australia opposes US position on extended patent protection for originator biologics as part of Trans-Pacific Partnership (TPP) deal

Following the breakdown of the latest round of Trans-Pacific Partnership (TPP)* talks in Hawaii, Australia’s Trade Minister Andrew Robb has confirmed that a major sticking point remains the US plan to enforce a 12-year period of exclusivity for originator biologics within all TPP partner nations, in line with the current US standard. This is considerably longer than the current patent protection periods in any of the TPP countries, which stand at a maximum of 8 years. In Australia – where patent protection lasts for only 5 years – there is particularly vocal opposition because the Australian government has a clear agenda to make biologic medicines more affordable by encouraging biosimilar competition. Mr. Robb signalled he would give no ground on the US stance that the term of protection for biologic drugs be extended beyond Australia's present 5 years. He commented, “You've got to set a balance somewhere between people getting a return on innovation and investment, and enabling competition to bring prices down for the rest of the community.”

Related articles 1>  2>  3>

See also UNITED STATES section

* The TPP is a proposed trade agreement between the US and several Pacific Rim countries (Australia, Brunei Darussalam, Canada, Chile, Japan, Malaysia, Mexico, New Zealand, Peru, Singapore and Vietnam). Its aims are to enhance trade and investment among the TPP partner countries in order to promote innovation, economic growth, and development.

EUROPE: EMA plans to revise guidelines for G-CSF biosimilars

The European Medicines Agency (EMA) has released a concept paper on its planned revision of specific guidelines for the non-clinical and clinical development of biosimilars containing recombinant granulocyte colony-stimulating factors (G-CSF). This guideline was one of the EMA’s first product-class specific biosimilarity guidelines and came into effect in February 2006. Since then, several biosimilar filgrastims have been licensed in the EU and it is proposed that the guideline needs updating based on the experience gained with their marketing applications, scientific advances and clinical use. The draft concept paper has been released for a 3-month consultation period and it is anticipated that the draft revised guideline will be released for consultation early in 2016.

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EUROPE: NICE issues guidance on introducing infliximab biosimilars into care pathways

The UK’s National Institute for Health and Care Excellence (NICE) has published a new resource to support the introduction of biosimilar versions of infliximab (Inflectra and Remsima) into clinical use. The resource has been developed for both clinical and non-clinical staff to help them manage the introduction of these biosimilar medicines into their care pathways safely and effectively. NICE maintains that biosimilar versions of infliximab have the potential to offer the UK National Health Service (NHS) considerable savings, especially when used to treat long-term conditions. The resource focuses on how NHS organizations can safely and effectively transition from originator infliximab (Remicade) to Inflectra or Remsima. It includes real-life insights from NHS clinicians who have already switched to these new products, providing:

  • Practical advice on how to effectively introduce biosimilars into the care pathway, taken from case studies carried out in two NHS Foundation trusts
  • Important advice on possible barriers to implementation and how to overcome these
  • Information on the opportunities for cost-savings and re-investment
  • A process to implement a well-managed safe switching program to biosimilars.
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GLOBAL: Meta-analysis of studies in nearly 1500 patients confirms safety of infliximab biosimilar

A major meta-analysis of clinical studies involving a total of 1454 patients treated with Celltrion’s infliximab biosimilar Remsima (for rheumatoid arthritis or ankylosing spondylitis) has shown that the safety profile of the biosimilar is consistent with that of the originator product Remicade (derived from historical data).

Adverse event incidence per 100 patient-years (95% CI)

Remsima (biosimilar)
n = 1454 (meta-analysis)

Remicade (originator)
(historical data)




Serious infections






Infusion reactions



The study findings add to accumulating evidence for the comparable safety of approved biosimilars versus originator biologics.

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Reference: Park W, et al. Paper #AB0433. Presented at: European League Against Rheumatism Annual European Congress of Rheumatology, June 10–13, 2015, Rome.

August 2015   +

GLOBAL: WHO issues clarified proposal for naming biologics

The World Health Organization’s (WHO) proposed biologic qualifier system is intended not just for biosimilars but for all biologics. Four random consonants will be assigned to all active biologic compounds but will not replace international non-proprietary names (INNs). Instead it would support INNs to ‘better harmonise international pharmacovigilance efforts’ and ‘avoid the proliferation of separate and distinct national qualifier systems.’

The WHO notes that some regulatory authorities have already decided that the use of a trade name and INN are adequate for prescription and dispensing and that, together with the batch number, these are sufficient for pharmacovigilance in conjunction with other tracking systems such as 2D barcoding. But the WHO aims to persuade undecided regulators such as the US FDA that the use of the biological qualifier (BQ) offers a means to not only uniquely identify the drug substance, but also to help with cross-checking other information in the absence of other sophisticated tracking systems.

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GLOBAL: Further evidence supports the clinical equivalence of biosimilar filgrastim

A biosimilar version of filgrastim has been shown to have comparable safety and efficacy to the originator Neupogen when used for the prevention of severe neutropenia in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy. In the Phase 3 study, 218 participants were randomly assigned to receive 1:1:1:1 non-alternating biosimilar or originator filgrastim or alternating treatments during each of six chemotherapy cycles. The results were published online ahead of print in the journal Annals of Oncology.1 These findings add to the mounting evidence that filgrastim biosimilars can be substituted for the originator. Last year a comparison of a biosimilar filgrastim (Nivestim) with Neupogen showed no statistical differences when used for the mobilization of peripheral blood stem cells in patients treated for hematological malignancies.

Related articles:  1>  2>

1. Blackwell K, Semiglazov V, Krasnozhon D, et alAnn Oncol 2015. [epub ahead of print].

GLOBAL: Stage is set for adalimumab biosimilars

Partners Merck and Samsung Bioepis cleared late-stage trials in rheumatoid arthritis with their biosimilar of adalimumab (Humira), the world's top-selling medicine, setting the stage for global regulatory applications as the originator comes off patent. According to a Bloomberg Intelligence survey, biosimilar copies of adalimumab are expected to be the most financially successful biosimilars to be launched in the US and Europe in the coming year.

Related articles:  1>  2>

GLOBAL: New biosimilars Facebook group is set up for healthcare professionals

A new Facebook group – the International Biosimilars Network (IBN) – has been established, describing itself as a growing community of global healthcare professionals interested in biosimilars.

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UNITED STATES: First US biosimilar will finally come to market in September

In response to a patent infringement lawsuit filed by Amgen, the makers of Neupogen (originator filgrastim), the US Court of Appeals for the Federal Circuit has ruled that Sandoz must wait until early September before it will be free to market Zarxio, the first US-approved biosimilar. This is in line with the requirement that a biosimilar manufacturer must give 180 days’ notice of the intention to bring their product to market. The patent dispute between Sandoz and Amgen has been ongoing since Zarxio received its FDA approval back in March.

However the court also ruled that Sandoz did not violate the law by choosing not to inform Amgen about its application to the FDA for approval of Zarxio or reveal its manufacturing intentions in advance. This communication of information – the so-called ‘patent dance’ – between biosimilar and originator companies was outlined in the Biologics Price Competition and Innovation Act (BPCIA) and Amgen had maintained it was mandatory. The court’s decision now makes it clear that it is optional – an important development for biotech companies hoping to introduce biosimilar products into the US. 

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UNITED STATES: ASCO endorses use of biosimilar filgrastim in updated guidelines

ASCO has updated its 2006 clinical practice guideline on the use of hematopoietic colony-stimulating factors (CSFs) in patients with cancer who are undergoing chemotherapy. Among other recommendations, the new guidelines stipulate that lower-cost biosimilars can replace originator filgrastim (Neupogen). ‘The lower-cost biosimilars are especially important in hospital use,’ the ASCO panel said.

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UNITED STATES: FDA expecting five biosimilar applications per year

The FDA says it is currently anticipating five applications for biosimilar approval per year based on the applications received in fiscal 2014. In a notice posted to the Federal Register, the agency says it expects each company to devote 860 hours per response. In addition, it expects two out of five of these applications to include additional submissions for interchangeability with an originator product. The FDA has also confirmed that it is still on track to issue draft guidance on demonstrating biosimilar interchangeability later this year. Three other biosimilars draft guidances – covering naming, labeling and statistical approaches to the evaluation of analytical similarity data – also are expected this year.

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UNITED STATES: Biosimilars Forum opposes CMS biosimilar reimbursement plans

The Biosimilars Forum (a nonprofit group representing US biosimilars manufacturers) is contending that, even though there may be several biosimilars based on the same originator drug, they should not be lumped into the same Medicare Part B reimbursement rate, which is what the Centers for Medicare & Medicaid Services (CMS) has now proposed. ‘The biosimilars statute and its legislative history make clear that each biosimilar product should be assigned a unique reimbursement code (commonly known as a J code),’ asserted Michael Werner, policy adviser to the Biosimilars Forum. ‘This is crucial to avoid confusion among healthcare professionals, to ensure that the correct prescribed products are dispensed to patients, and to allow a fair and predictable reimbursement to purchasers of biosimilars.’

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EUROPE: Leading French hospital group chooses biosimilar infliximab at 45% discount

A biosimilar version of infliximab has won a major tender in France for treating patients with rheumatoid arthritis, Crohn's disease and psoriasis. The central purchasing agency for the Assistance Publique - Hôpitaux de Paris (AP-HP) – which caters for nearly 25% of the population of France – said it had decided to opt for the biosimilar after Hospira offered a discount of 45% compared to the originator Remicade. This has prompted widespread speculation over future pricing of biosimilars.

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ASIA-PACIFIC: Australian Department of Health convenes major biosimilars consultation meeting

In light of the ongoing controversy in Australia over the plan to allow pharmacists to substitute biosimilars for originators without clinical supervision, the Australian Department of Health has convened a major consultation meeting involving more than a dozen stakeholder organizations representing consumer, clinician and industry groups. The meeting is being held in Sydney on the eve of a meeting of the Pharmaceutical Benefits Advisory Committee (PBAC), at which the PBAC will consider an application for its first biosimilar infliximab candidate as well as a second submission for Lilly’s biosimilar insulin glargine, Basalgar.

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ASIA-PACIFIC: Council of Australian Therapeutic Advisory Groups issues guidance on biologic and biosimilar usage

The Council of Australian Therapeutic Advisory Groups (CATAG) has issued new guiding principles on good governance and decision-making with respect to the use of biologic/biosimilar therapies within Australian public hospitals. CATAG says the principles in the guidance should be considered in totality and not in isolation. They are intended to provide an overall framework for choosing first-line therapies and potentially switching patients from one biologic product to another under the auspices of a Drugs and Therapeutics Committee and individual hospitals’ governance processes. The CATAG principles will be revisited in line with evolving international recommendations.

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ASIA-PACIFIC: Push by Indian biotech companies to make their mark on biosimilars market

Pharma companies within India’s leading industrial state of Gujurat are increasingly focused on the biosimilars market, which is expected to grow locally by 30% per year through 2018. Among firms in Gujarat, Intas Pharma last week launched a domestic biosimilar of Novartis’ eye drug ranibizumab (Lucentis). Intas’ first biosimilar, Accofil (filgrastim) was launched in Europe earlier this year and the company expects to launch its first biosimilar in the US within 9–12 months. But an Intas spokesperson said, “cracking regulated markets for biosimilars is not an easy task.”

Related articles:  1>  2>

July 2015   +

GLOBAL: Real-world data show success of switching from originator biologic to biosimilar

Results presented at this year’s European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology in Rome (June 10–13) showed that, during the course of 11 months, patients experienced similar effectiveness and safety after switching from originator infliximab (Remicade) to a biosimilar version, Inflectra. Thirty-nine patients who had been stable on Remicade for an average of 4 years were switched to Inflectra with no unexpected side effects or loss of efficacy reported by any participants. A much larger switching study (NOR-SWITCH), which is ongoing in 500 patients in Norway, is expected to report next year.

Related abstract>

GLOBAL: WHO – Debate over biosimilar naming may be coming to a head

The World Health Organization (WHO) is about to embark on a series of meetings to decide upon the best approach for naming biosimilars. The central question is whether biosimilars should be given the same international non-proprietary name (INN) as originator biologics and, if not, exactly how they should be differentiated. The issue has divided drug makers, healthcare providers and other stakeholders: some argue that different names would simply confuse prescribers and patients while others insist different names are essential for product tracking as part of pharmacovigilance. The European Medicines Agency (EMA) has so far given licensed biosimilars the same INNs as their originators, but does require all biologics to be identified by brand name and batch number. In the US, the first approved biosimilar, Zarxio, has been given an INN with a company-specific suffix ‘filgrastim-sndz’ to distinguish it from the originator. This has led some to suggest that originators should also have suffixes and the WHO is considering a system which would assign a four-letter alphabetical code to all biologics. One point on which there is broad agreement is that a final resolution to the naming issue is needed soon.

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UNITED STATES: “The unsustainably high prices of cancer drugs is a big problem, and it’s our problem.”

In a high-profile speech at this year’s ASCO (American Society of Clinical Oncology) meeting in Chicago (May 29–June 2), which attracted 25,000 delegates, Memorial Sloan Kettering Cancer Center oncologist Leonard Saltz broke with convention by criticizing drug costs within his plenary address. "These drugs cost too much. The unsustainably high prices of cancer drugs is a big problem, and it’s our problem,” Dr. Saltz said. In an interview prior to his speech, Dr. Saltz commented that there has been a taboo associated with doctors talking about drug prices, in part because doctors are expected to focus on what’s best for patients regardless of costs. But he pointed out that, in recent years, drug prices have begun to more significantly impact healthcare, with patients often expected to pay a percentage of the cost for high-priced therapies. This has forced some patients to forego effective therapies because of the financial burden. “All of the stakeholders involved need to stop pretending that price is something we don’t need to discuss, because it affects all of us, and it’s affecting our ability to deliver quality care to everyone,” Dr. Saltz said.

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UNITED STATES: US prescribers urge the FDA not to label biosimilars like generics

One of the FDA’s recent biosimilar guidance documents has drawn criticism for eliminating labelling information which clearly identifies a product as a biosimilar as opposed to an originator. The 2012 draft of the guidance specified that the labelling should make this clear, in addition to indicating whether the product has been approved as ‘interchangeable’ with the originator. However, this requirement has been omitted from the latest version of the guidance. The label for the first approved US biosimilar, Zarxio, does not mention the word ‘biosimilar’ and cites data from pivotal studies with originator filgrastim.

In May, nine organizations representing physicians who routinely prescribe biologics, including the American Association of Clinical Endocrinologists and American College of Rheumatology, sent a letter urging the FDA not to employ ‘a generic-like approach’ to labelling for biosimilars as it appears to have done with Zarxio. Their view is that clinicians should be aware if a product is an originator or a biosimilar to enable informed prescribing choices. A Capitol Hill panel of physicians and advocates hosted by the Alliance for Patient Access has expressed similar concern.

Related articles: 1>  2>

UNITED STATES: Confidence in biosimilar TNF inhibitors grows among US prescribers

Of 192 rheumatologists and gastroenterologists polled in the US last week, 81% said that, over the past 12 months, they have become more positive about the idea of prescribing biosimilar TNF inhibitor products when these come to market. Convincing switching data is viewed as a key catalyst for uptake.

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UNITED STATES: Biosimilars – "Ready, Set, Launch"

The Academy of Managed Care Pharmacy (AMCP) has convened a group of healthcare thought leaders from across the country to discuss issues surrounding the marketplace readiness, acceptance and utilization of biosimilars. The AMCP Partnership Forum, “Biosimilars: Ready, Set, Launch,” met in June to explore how managed care pharmacy can work with other key stakeholders to ensure a smooth launch of biosimilars for patients, providers and payers alike. “We are at a unique moment in history,” said AMCP CEO Edith A. Rosato. “Rarely has the health care sector witnessed the introduction of a completely new class of therapeutic products. The arrival of biosimilars – much like the introduction of generic drugs decades ago – will provide patients and providers with safe, effective and more affordable therapeutic alternatives for treating some of the most pernicious chronic diseases."

Related article>

EUROPE: 70% discount made available on infliximab biosimilar in Denmark

Norway is no longer the only European market where biosimilar infliximab is selling at an ‘extraordinary’ discount versus the branded product. In Denmark this biosimilar has been made available at a 70% discount. Clinicians in Danish and Norwegian hospitals can now treat a patient for 3 years with biosimilar infliximab for the same price as 1 year with the originator. The tender process in these countries has been followed closely by drug companies and other national governments and may set guidelines for the pricing of biosimilars across Europe. 

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EUROPE: EULAR issues position paper to explain biosimilars to patients

The European League Against Rheumatism (EULAR) has established that many patients are anxious about being treated with biosimilar drugs and need access to clear information about trial data to allay their fears. EULAR has issued a position paper which seeks to explain the concepts in plain wording, and calls on the scientific community to provide ‘timely lay summaries of all results of relevant and important studies’ to patients.

Related position paper>

EUROPE: Spanish Society of Rheumatology supportive of biosimilars

The Spanish Society of Rheumatology has issued a position statement on biosimilars, reflecting its views on issues such as interchangeability and traceability. It states that it is committed to the sustainability of the healthcare system in Spain but also considers it is ‘essential to preserve physicians’ freedom to prescribe the drug(s) best suited to the characteristics and circumstances of each patient.’ The Society has offered to carry out safety monitoring studies for biosimilars, given its extensive experience with pharmacovigilance registries.

Related abstract>

EUROPE: UK’s NICE recommends infliximab biosimilars ahead of originator

The UK’s National Institute for Health and Care Excellence (NICE) is recommending two biosimilar versions of one of the world's biggest-selling drugs, infliximab, and says that these more affordable options should be used ahead of the originator. The decision is still subject to consultation, with final NICE guidance expected to be published in October. NICE’s recommendation is based on the fact that regulators have already deemed these biosimilars to be bioequivalent to the originator product.  For this reason, the NICE appraisal committee has not re-assessed the products’ comparability data but has endorsed them on the basis of their lower cost. Some UK prescribers remain uncertain about biosimilars but if NICE does recommend them in its final version of this guidance then the National Health Service (NHS) in England will be duty-bound to use them ahead of the originator under new formulary rules.


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ASIA-PACIFIC: Concerns voiced about Australian biosimilars pharmacy-level switching policy

Within Australia and elsewhere, major concerns have been expressed about the Australian Pharmaceutical Benefits Advisory Committee (PBAC) statement that pharmacy-level switching of originator biologics for biosimilars would be its default position. The Australian Department of Health did subsequently emphasize the importance of interchangeability data to support switching, but it appears that the PBAC intends to allow switching in the absence of these data. The CEO of AusBiotech, the organization representing Australian biotech manufacturers, has written to the Australian Health Minister Sussan Ley expressing opposition to this. In the US, the Alliance for Safe Biologic Medicines (ASBM) indicated that the PBAC position means that Australia would break with widely held international standards by becoming the first and only nation to allow pharmacy-level substitution of biologic medicines without physician involvement.

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LATIN AMERICA: Brazil approves first biosimilar via its ‘comparability’ approval pathway

Brazil’s National Health Surveillance Agency (ANVISA) has approved its first biosimilar via its ‘comparability’ approval pathway, which is in alignment with international standards for biosimilar approval. ANVISA currently has two biosimilar approval pathways: the second one – known as the ‘individual development pathway’ – is not based on comparisons with originators and requires a full dossier of data. The newly licensed product Remsima (a biosimilar of infliximab) is indicated for a number of conditions including Crohn’s disease and ulcerative colitis, and is also the first biosimilar monoclonal antibody approved in Brazil. 

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June 2015   +

Major European congress highlights need for a sustainable biosimilar market

The European Generic and Biosimilar Medicines Association held its 13th annual European biosimilars conference on 23–24 April in London. Developing a sustainable European biosimilars market was a major focus of the conference – as well as the potential cost of failing to do so. Key areas for discussion were:

  • Biosimilars of a number of major biologics used in oncology and rheumatic diseases are expected to come to market in the next 3 years. In the context of aging populations and the growing incidence of chronic diseases, harnessing the potential of biosimilars to deliver savings and broaden patient access to these treatments is essential.
  • The arrival of new biologics for diseases traditionally treated with small-molecule drugs (e.g. PCSK9 inhibitors for lowering cholesterol) is expected to create new demands on healthcare budgets. Savings from the use of biosimilars are needed to fund these new classes of treatment.
  • In most EU countries, well-established biosimilars have gained substantial market share. Portugal, Norway, and Poland have experienced particularly rapid uptake. In Poland, biosimilar penetration is driven by its tendering system and by the Polish Ministry of Health’s encouragement of automatic substitution (assuming interchangeability) at all treatment stages. In Italy, where caution initially prevailed, growing confidence in established biosimilars has been reinforced by growing concerns for sustainability. In contrast, biosimilars have struggled for adoption in Belgium,* Ireland, and France, where they face complex regulatory issues and other challenges.

*See ‘Barriers to biosimilar uptake – focus on Belgium’ in Journal digest section.

Read the full article >>

New EMA guidelines allow use of non-EU originator data to avoid trial repetition

On 30 April 2015, a new EU Guideline on biosimilar medicines took effect. First seen in draft form in 2013, the new Guideline replaces the original 2005 version. The most significant change is that developers of new biosimilars are now permitted to file for EU approval using data from certain clinical trials conducted with non-EU authorized originator products (so-called ‘foreign bridging data’). This development avoids unnecessary repetition of trials.

Read the full article >>

Learn more about biosimilars in Europe >>

FDA issues further biosimilar guidance

At the end of April the FDA finalized two guidance documents, covering quality and scientific considerations in demonstrating biosimilarity, and an industry Q&A (all originally drafted in 2012). They also issued an additional draft Q&A document in May. The latest guidance indicates a degree of flexibility in that – under certain circumstances – a candidate biosimilar may have a different formulation, delivery device, or container closure from the originator. The guidance also describes conditions in which a sponsor may cite comparative data with a non-US-licensed product or extrapolated clinical data designed to support a different condition of use. The new draft Q&A document provides specific information such as the number of samples to be held in reserve after clinical testing and how to demonstrate that a biosimilar has the same dosage form as the originator. However, many additional questions remain – including the criteria for demonstration of interchangeability and finalized policies for biosimilar naming and labelling. On 21 May the FDA confirmed that they are on track to release guidance on naming, labelling and interchangeability by the end of this year, along with recommendations on statistical approaches to evaluating analytical similarity data.

To learn more, read these full articles:

Zarxio: launch update

A US federal circuit court has granted a request by originator manufacturer Amgen to temporarily block sales of Sandoz’s Zarxio, the first FDA-approved biosimilar. Amgen’s injunction means that Zarxio cannot be marketed, sold or imported into the US until the court resolves a legal dispute between the companies related to potential patent infringement.

Read the full article >>

Brazilian academic societies deliver shared viewpoint

The Brazilian Society of Rheumatology, Brazilian Society of Dermatology, Brazilian Federation of Gastroenterology and Brazilian Study Group on Inflammatory Bowel Disease released a joint paper recommending the use of biosimilars for the treatment of autoimmune conditions to increase access to biologic treatment and reduce costs for healthcare systems. They specifically recommend that:

  • physicochemical and preclinical comparability exercises follow the WHO guidelines
  • biosimilarity is demonstrated via clinical equivalence studies with adequate margins
  • pharmacovigilance should be as rigorous as with originator biologics
  • nomenclature should distinguish biosimilars from originators for product tracking
  • substitution by pharmacists requires prescriber consent.

See full article >> Valderílio Feijó Azevedo et al. Available online from Autoimmunity Reviews.

Australian PBAC may allow substitution without prescriber notification

The Australian Pharmaceutical Benefits Advisory Committee (PBAC) – which decides what products will be eligible for government subsidy via the Pharmaceutical Benefits Scheme (PBS) – is considering earmarking individual biosimilars as ‘equivalent’ to their originator biologics. This so-called “a” flagging, allocated on a case-by-case basis, would enable pharmacists nationwide to substitute certain biosimilars for originators, in the same way generics are substituted for branded chemical drugs without prescriber notification. But the regulatory authority, Medicines Australia, said biosimilar interchangeability should be the regulator’s decision. Meanwhile, the first biosimilar insulin approved in Australia has been included in the PBS list.

Read the full article >>

Potential impact of biosimilars on healthcare costs and patient access

  • Researchers in Europe have published a simulation study predicting the economic effects of substituting biosimilar filgrastim for the originator biologic in the management of chemotherapy-induced febrile neutropenia within the EU G5 countries. Significant cost savings were predicted as well as increased access to targeted antineoplastic treatment.1 The study design and findings are in line with a similar simulation study published last year on use of biosimilar epoetin for anemia.2
  • Nearly 50% of oncologists surveyed in the US, Mexico, Turkey, Russia, and Brazil reported that they would increase the use of HER2 monoclonal antibody therapy for HER2+ breast cancer across all treatment settings if a lower cost biosimilar of trastuzumab was available.3

1. Sun D et al. Clin Ther. 2015;37(4):842–57. 
2. Abraham I et al. Future Oncol. 2014;10(9):1599–609. 
3. Lammers P et al. Pharma (Basel) 2014;7(9):943–53. 

Biosimilar giants launch Biosimilars Forum to support public policy

On 5 May, leading biosimilar developers in the United States announced the launch of the Biosimilars Forum to support public policies and practices that encourage access, awareness, and adoption of biosimilars. The forum was developed by 11 pharma and biotech companies with significant biosimilars development portfolios.

Read the full article >>

Barriers to biosimilar uptake: focus on Belgium

  • Biosimilar uptake has been slow in Belgium compared with most other EU countries. A Belgian research group analyzed the situation and reviewed possible prescribing incentives used in five other EU countries (France, Germany, the Netherlands, Spain, and Sweden). Potential incentives and constraints identified included prescription quotas/targets, clinical guidelines, primary substitution, reference price system, fixed payment and public tendering. They propose further studies to evaluate the effectiveness of these measures.4
  • A second research group conducted interviews with a number of stakeholders in Belgium regarding slow biosimilar uptake and identified three key barriers: a lack of confidence in biosimilars, uncertainty about interchangeability, and a hospital financing system that discourages biosimilar use. Focused educational programs for prescribers and payers, reform of healthcare financing and introduction of prescribing incentives (e.g. biosimilar prescription quotas and efficient reimbursement) were the main suggested solutions. Establishment of biosimilar patient registries was also proposed.5

4. Swartenbroekx N et al. J Pharm Belg. 2014;Dec(4):36–46. 
5. Dylst P et al. Pharmacoecon 2014;32(7):681–91.

At the end of April the FDA finalized two guidance documents, covering quality and scientific considerations in demonstrating biosimilarity, and an industry Q&A (all originally drafted in 2012). They also issued an additional draft Q&A document in May. The latest guidance indicates a degree of flexibility in that – under certain circumstances – a candidate biosimilar may have a different formulation, delivery device, or container closure from the originator. The guidance also describes conditions in which a sponsor may cite comparative data with a non-US-licensed product or extrapolated clinical data designed to support a different condition of use. The new draft Q&A document provides specific information such as the number of samples to be held in reserve after clinical testing and how to demonstrate that a biosimilar has the same dosage form as the originator. However, many additional questions remain – including the criteria for demonstration of interchangeability and finalized policies for biosimilar naming and labelling. On 21 May the FDA confirmed that they are on track to release guidance on naming, labelling and interchangeability by the end of this year, along with recommendations on statistical approaches to evaluating analytical similarity data.

To learn more, read these full articles:

May 2015   +

CVS Health Corp predicts 40–50% savings from biosimilars

CVS Health Corp’s Chief Medical Officer says he expects biosimilar savings in the US to amount to as much as 40–50% – higher than originally predicted – but added that estimates depend upon the extent of competition, level of biosimilarity, and prescriber/payer attitudes toward biosimilar drugs.

Read the full article >>

Generic Pharmaceutical Association launches Biosimilar Council

The US Generic Pharmaceutical Association (GPhA) has established a dedicated Biosimilar Council that will work to ensure a positive regulatory, reimbursement, political, and policy environment that supports access to biosimilars. The Council, which includes manufacturers and stakeholders, will also serve as an educational resource for the public. A similar initiative has been launched by the GPhA’s counterpart body in Canada.

To learn more, read these related articles:

Medicare and Medicaid outline reimbursement plans favoring biosimilars

On March 31, Centers for Medicare and Medicaid Services (CMS) removed an incentive for physicians to prescribe more expensive Medicare Part B originator drugs in a move to encourage preferential biosimilar prescribing. They also opened the door to formulary exclusions of originator drugs under Medicare Part D, which is required to offer at least two distinct drugs in each class. CMS said it would not consider a biosimilar and an originator product as different drugs to satisfy that requirement, making it easier for plans to exclude originator drugs.

Read the full article >>

US focuses on commercialization issues in wake of first biosimilar approval

Following the FDA’s recent approval of Zarxio, the first US biosimilar, the issues surrounding its forthcoming commercial launch continue. The Biologics Price Competition and Innovation (BPCI) Act originally envisaged that biosimilar applicants and originator manufacturers would engage in a series of goodwill exchanges of patent-related information – colloquially known as the ‘patent dance’ – which would help to avoid subsequent lawsuits around potential patent infringement. Sandoz, the manufacturer of Zarzio, chose not to do this in view of the time that it might take, and the ensuing legal proceedings have established that avoiding the patent dance is permissible. In addition the FDA has confirmed that biosimilar applicants need not disclose their application details to originator manufacturers prior to FDA submission. Although Amgen – the originator manufacturer – has appealed, it appears that Sandoz is not obliged to wait for the appeals court decision before launching Zarxio. These events indicate that the path to launching new biosimilars in the US may involve fewer hurdles than originally thought. Meanwhile, debate continues regarding the non-proprietary naming of biosimilars, biosimilar labelling transparency, and substitution of interchangeable biosimilars by pharmacists without prior prescriber notification.

To learn more, read these full articles:

IAPO educates patients about biosimilars across Latin America

The International Alliance of Patients’ Organizations (IAPO) has launched a new online resource on biologic and biosimilar medicines for patients in Latin America. Available in English, Spanish, and Portuguese, IAPO hosts a range of resources, events, and blogs to ensure that patients are informed and their voices are heard.

Read the full article >>

Mexico requires 23 approved ‘copy biologics’ to reapply as ‘biosimilars’

The Mexican regulatory body COFEPRIS has announced that all ‘copy biologics’ licensed before 19 October 2011 – when Mexico issued formal biosimilarity guidelines – will have to re-apply as candidate biosimilars and conduct all clinical studies required to comply with rigorous international standards. Re-application as biosimilars is required by the end of 2015.

Read the full article >>

Biosimilar infliximab may significantly increase access to RA biologic treatment in Central and Eastern Europe

Hungarian researchers estimate that introduction of biosimilar infliximab within six Central and Eastern European countries (CEE) could allow 1,205 additional patients with rheumatoid arthritis (RA) to receive biologic therapy and up to 1,790 if interchangeability is permitted. The authors consider this significant as the current average access rate to biologics for RA in CEE countries is approximately 5.3% compared to 19.1% in Western and Southern Europe.

Read the full article >>

EMA expands biosimilar insulin guidance

The EMA has expanded its 2006 guideline on biosimilar insulins to include intermediate- and long-acting insulin preparations and to provide more detail on study design requirements and safety investigations.

  • Specific efficacy studies will not be required because commonly used endpoints, such as HbA1c (glycated hemoglobin), are not sensitive enough for biosimilarity studies.
  • Safety studies should be performed with a specific focus on immunogenicity and should include patients with type 1 diabetes.
  • Satisfactory demonstration of biosimilarity with subcutaneous use should allow extrapolation to intravenous use, if applicable, and to other indications and patient populations licensed for the originator.
  • The requirement for manufacturers who are planning comparative insulin-clamp studies to “consider reports that individuals of African, South Asian or Hispanic descent have reduced glucose clearance” has been dropped following agreement that, because each subject is their own control, ethnic differences should not matter.
  • It remains a requirement for comparator originator products to be sourced from within the European Economic Area.

To learn more, read these full articles:

Biosimilar investment increases in China

China looks set to enhance its presence in the biosimilar space with the news that Innovent, a leading Chinese biotech company, has raised USD $100m in venture cash in the hope of becoming the premier biosimilar supplier in the country. In addition, in a rare deal between Eastern and Western pharma companies, Innovent has struck a $456m oncology partnership with Eli Lilly focused on both biosimilars and innovative biologics. However, at present, South Korea and India remain the biosimilar leaders in Asia and will likely dominate in the region for some time, according to local analysts.

To learn more, read these full articles:

Chinese regulators finalize biosimilar guidelines

The China Food and Drug Administration (CFDA) issued its official biosimilars guidance in February. The final version (a revision of a draft first released in November 2014) stipulates that biosimilars will follow an existing approval pathway used for novel biologics, but their technical review process will abide by a distinct set of principles. Originators used for comparison may be products licensed in China or elsewhere, as long as they are approved in China by the time biosimilar clinical development begins. The rigor of the Chinese guidance aligns with that of the EMA and US Food and Drug Administration (FDA), and signals the CFDA’s intention to develop biosimilars that are on a par with Western standards.

Read the full article >>

April 2015   +

FDA approves first US biosimilar

Sandoz’s Zarxio, a biosimilar of filgrastim, became the first FDA-approved biosimilar on 6 March. “Biosimilars will provide access to important therapies for patients who need them. Patients and the healthcare community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy and quality standards.” – FDA Commissioner Margaret A. Hamburg, MD Read the full article >>

  • FDA approval of Zarxio was extrapolated to include all 5 licensed indications of the originator
  • Zarxio’s prior EU approval and track record of >7.5 million days of patient exposure eased the way for its FDA approval Read the full article >>
  • Zarxio’s label mirrors that of the originator and cites the safety and efficacy data from the originator’s clinical trials
  • Zarxio has been given a temporary non-proprietary name – ‘filgrastim-sndz’ – combining the originator’s non-proprietary name with a company-specific suffix
    Courts deny motion for a preliminary injunction – an anticipated obstacle for manufacturers of new biosimilars because biologics can be protected by complex patents – but an appeal may still delay the launch of Zarxio. Read the full article >>

    Interchangeability – FDA calls for industry input on guidance

    Zarxio has not been approved as ‘interchangeable’ – a status that would provide exclusivity for biosimilars, but requires more data from applicants. The FDA has reached out for industry comments on the data required for interchangeability via the 351(k) pathway. Applicants will need to demonstrate that their product can be expected to produce the same clinical result as the originator in any given patient, and that the risks of switching between their product and the originator – without prescriber intervention – will not exceed those of using the originator throughout.

    Read the full article >>

    Naming – FDA decision on non-proprietary naming of biosimilars still pending

    For approved biosimilars, some stakeholders support the use of a non-proprietary name identical to that of the originator (the convention in the EU) to avoid confusion among prescribers, pharmacists, and patients; others caution that distinguishable names are important for pharmacovigilance, allowing any adverse events to be traced to a particular product. With the placeholder name ‘filgrastim-sndz’, the FDA has opted for a compromise but has pointed out that the name is not final.

    Read the full article >>

    Pharmacist substitution – Individual states retain decision-making power

    Even if a biosimilar is approved as ‘interchangeable’ by the FDA, individual states retain decision-making power on pharmacist substitution. Eight states have now empowered pharmacists to dispense a biosimilar in place of an originator but with variations: for example, Indiana only allows a biosimilar substitution if the prescriber writes “may substitute” on the prescription. Utah, North Dakota and Oregon all require the pharmacist to notify the prescriber of the substitution within 1 to 3 days. Colorado's biosimilars bill – which now needs only a governor's signature to become law – takes the prescriber notification issue a stage further. Under their bill, pharmacists will only need to notify prescribers of a switch if no electronic database is available to make note of this. Otherwise, the prescribing physician will only learn that a patient has been switched if they check the database.

    To learn more, read these full articles:

    Potential US market growth – FDA predicted to approve nine biosimilars by 2020

    Tufts Center for the Study of Drug Development predicts that nine biosimilars will have FDA approval by 2020, but that the lack of familiarity with biosimilars among physicians – and arrival of innovator biologics in the same therapeutic classes – may slow uptake. However, potential prescriber hesitance may be countered by payers who are expected to encourage biosimilar prescribing by offering lower co-pays for patients taking biosimilars instead of originators.

    Read the full article >>

    March 2015   +

    US Food and Drug Administration (FDA) panel unanimously recommends approval of cancer treatment biosimilar

    “A historic occasion” is how Janet Woodcock, FDA Director of the Center for Drug Evaluation and Research, described a review meeting of the Oncologic Drugs Advisory Committee (ODAC) held on 7 January 2015. ODAC advises the US FDA on regulatory decisions related to cancer drugs and its 14 members “unanimously recommended” that the FDA should approve EP2006, a biosimilar of Neupogen (filgrastim), which is licensed for the treatment of neutropenia. Developed by Sandoz, EP2006 is expected to win final FDA approval shortly, making it the first biosimilar to enter the US market. Express Scripts, the largest pharmacy benefits manager in the USA, estimates that the introduction of EP2006 alone “could save $5.7 billion in drug costs over the next 10 years.”

    Read the full article >>

    What the FDA panel vote on a biosimilar says about approvals

    "A landmark decision" is how the Wall Street Journal described the FDA panel’s vote. But their correspondent noted that the meeting “also provided some important clues for drug makers as they try to gauge the hurdles needed to be cleared for FDA approval.” According to the report, the panel probed deeply on issues such as minor differences in clinical data and just what range of bioequivalence should be permitted. Evidence of long-term safety was a major consideration. And although they recommended that the biosimilar version of filgrastim could be used for all of the originator’s licensed indications (which is termed ‘extrapolation’), this won’t be inevitable for other biosimilars.

    BIO urges FDA to release guidance on biosimilars

    Meanwhile the Biotechnology Industry Organization (BIO) has called on the FDA to release final guidance on processes and scientific criteria for the approval of biosimilars, outline its approach to naming and labelling, and clarify its conditions for determining a biosimilar to be interchangeable with its originator. BIO believes the best way to develop policy in this field is “through published guidance documents with the opportunity for public comment, rather than through single-application advisory committee meetings.”

    Read the full article >>

    New biosimilar FDA guidance coming in 2015

    It’s possible that BIO will get their wish for greater clarity on FDA policy later this year. The FDA’s Center for Drug Evaluation and Research (CDER) has released a new list of guidance documents it plans to publish in 2015. Four of these documents focus on biosimilars, and topics include how biosimilar products should be labelled and the regulatory considerations for demonstrating interchangeability with a reference product. Guidance documents, unlike regulations, serve to clarify how the FDA expects to enforce regulations, not set new ones.

    Read the full article >>

    Substitution allowed? State biosimilar laws are evolving

    In the USA, state law governs the ability of a pharmacist to make substitutions for a prescribed branded drug and to decide whether or not to dispense a generic version. The same will apply in the case of biosimilars. Currently, only eight states have enacted biosimilar substitution laws and these are relevant only for biosimilars designated ‘interchangeable’ by the FDA. These interchangeable products must meet higher standards, including proof that there is no greater risk in switching to the biosimilar as compared with continuing use of the originator.

    Read the full article >>

    UK’s NICE updates process for reviewing biosimilars

    In anticipation of the increasing availability of biosimilars, the UK’s cost-effectiveness review body NICE (National Institute of Health and Care Excellence) has updated its methods for reviewing biosimilar applications. Applications for national biosimilar funding will be reviewed under a ‘multiple technology appraisal process’ along with the originator, according to a position statement released on 6 January. “Biosimilars have the potential to offer the National Health Service considerable cost savings, especially as they are often used to treat long-term conditions,” NICE noted.

    Read the full article >>

    October 2014   +

    European Medicines Agency approves first insulin glargine biosimilar in the European Union and FDA grants tentative approval for insulin glargine

    On September 10, 2014, the European Medicines Agency (EMA) granted marketing authorization to Lilly and Boehringer Ingelheim for Abrasia for the treatment of Type I and Type II diabetes mellitus via the biosimilars pathway. Abrasia has the same amino acid sequence as Sanofi’s Lantus (reference product) and will be the first biosimilar of insulin glargine available on the European market.

    The Committee for Medicinal Products for Human Use (CHMP) plays a vital role in the marketing procedures for medicines in the European Union and is responsible for preparing opinions on questions concerning medicines for human use. The CHMP opinion stated that ‘studies have shown Abrasia to have a comparable quality, safety and efficacy profile to Lantus (insulin glargine).’ Eli Lilly will be required, as with all biologics, to implement a pharmacovigilance plan as part of the marketing authorization.

    This approval is good news for patients with diabetes in Europe, especially after the disappointing withdrawal of previous applications for three biosimilar insulin products by Marvel Life Sciences in November 2012.

    The US Food and Drug Administration (FDA) granted tentative approval for Lilly and Boehringer Ingelheim’s insulin glargine in August of this year with the provisional trade name of Basaglar. This product was approved through the 505(b)(2) pathway, which is an abbreviated drug approval pathway for versions of existing drugs and some protein products.

    Read the full article

    USA accepts first application for biosimilar approval under new 351(k) pathway

    Biopharmaceutical company Sandoz, a Novartis subsidiary, has filed the first-ever biosimilar application in the USA with the FDA using its 351(k) pathway. Sandoz's announcement in July 2014 noted the ‘FDA has already accepted filing for a biosimilar Neupogen (filgrastim), an FDA-approved treatment used to decrease rates of infection in patients with non-myeloid malignancies who are already receiving chemotherapy.’ This drug could become the first US-approved biosimilar via the 351(k) pathway, and may be a cheaper version of its reference product.

    The US Congress passed a law to enable future approval of biosimilars nearly four and a half years ago and Sandoz's application is the first one to be submitted for full marketing approval under the 351(k) pathway. Sandoz noted ‘this is a significant step toward making high-quality biologics more accessible in the USA.’

    The approval of this first biosimilar could indicate how biosimilar products will be priced compared with their reference products. At the time of the passage of the Biologics Price Competition and Innovation Act (BPCA) in 2009, congressional budget forecasters anticipated that biosimilar drugs could save consumers and the federal government billions each year by boosting market competition. However, considering the complexity of biosimilar development, some analysts suspect that savings may be much lower than anticipated for US consumers.

    If approved, Sandoz’s biosimilar will be marketed with the brand name Zarzio and will help the FDA further define the criteria for ‘similarity’ for future applications and guide aspects of commercialization.

    Read the full article

    New FDA draft guidance: Reference product exclusivity for biological products filed under Section 351(a) of the PHS Act

    The FDA released Guidance for Industry on August 8, 2014 to address the 12-year period of exclusivity granted for reference products under section 351(a) of the Public Health Service (PHS) Act as amended by the Biologics Price Competition and Innovation Act of 2009.

    The Guidance states that the FDA may not grant licensure to a biosimilar or interchangeable product for a 351(k) application until 12 years after the reference product was first licensed. In addition, the FDA may not accept a 351(k) application for review until 4 years after the reference product was first licensed.

    The BPCA provisions state that not every licensure of a biologic filed under 351(a) is considered a ‘first licensure’ giving rise to a 12-year period of exclusivity. A 351(a) licensure does not qualify for exclusivity if it is a supplement to the already approved reference product or a subsequent application filed by the same sponsor or manufacturer of the biological product for:

    • a change (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength; or 
    • a modification to the structure of the biological product that does not result in a change in safety, purity or potency.

    The guidance document is intended to represent current FDA thinking and public comments were invited.

    Read the full article

    July 2014   +

    Safety concerns related to biosimilars drug development

    The following article from the Quintiles Global Biosimilars Unit was published in the June 2014 issue of the Regulatory Affairs Professionals Society’s Regulatory Focus.

    Written by Drs Raymond Huml MS, DVM, RAC, Executive Director and Nigel Rulewski, MD, DCH, DRCOG, Vice President, the article identifies five major scenarios that could result in untoward safety signals – such as immunogenicity – during biosimilar drug development and marketing.

    Dr. Rulewski states, “as an increasing number of highly successful biologics are coming off patent, biosimilars remain a promising area for continued investment. With lucrative first mover advantages in the larger markets, companies are keen to be the first to market.”

    Dr. Huml concurs that speed is driving business strategy and mentions that, “the intense focus on speed to market for biosimilar developers has resulted in a regulatory disparity among countries with regard to global biosimilar drug development programs.”

    The article mentions that, although an unfortunate safety experience occurred early in the development of biologics (not with a biosimilar product), biosimilar drug development has proven safe over a time span of more than a decade, despite wide regulatory variance among different geographies. On one hand, in the USA, biosimilar drug development has not yet resulted in any approvals via the 351(k) pathway. On the other hand, driven primarily by the desire to bring less expensive biologic options to their citizens, many other countries are forging ahead. These countries are advancing and approving biosimilars. Given this variable regulatory landscape, there is the possibility for an untoward safety signal, which could result from or be impacted by:

    • marketing approvals based on small clinical trials
    • outsourcing of manufacturing
    • pressure for speed to market
    • trials in emerging markets
    • lack of specific regulatory guidance and biosimilar approvals in the USA.

    To access the full article, please click here. If you are not a member of the Regulatory Affairs Professional Society, please contact us to request a copy.

    FDA draft guidance to assist biosimilar sponsors in designing clinical pharmacology studies

    On May 13, 2014, the FDA released a draft guidance entitled Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product.

    This guidance is one of a series intended to assist biosimilar pharmaceutical companies in designing clinical pharmacology studies used to support 351(k) and 505(b)(2) applications.

    Three key concepts, including 1) the exposure and response assessment, 2) the evaluation of residual uncertainty and 3) the analytical quality and similarity, are discussed in more detail.

    The result of the comparative analytical characterization, according to the FDA guidance, will result in one of four possible assessments for regulatory approval: not similar, similar, highly similar, and highly similar with fingerprint-like similarity. Possible ramifications for these designations include consideration of another approval pathway if not similar, and the amount and type of analytical, non-clinical (animal), and clinical comparability testing required prior to US approval.

    Regarding biosimilar safety data, the “FDA recognizes that safety and immunogenicity data derived from these studies may need to be supplemented by additional evaluations either pre- or post-approval” and, while not surprising for those involved directly or indirectly in discussions with the FDA, the document formally recognized that “human PK and PD studies should be conducted in healthy volunteers if the product can be safely administered to this population.”

    It was unclear what guidance will be issued next and when biosimilar guidelines will be available that discuss substitutability and interchangeability with the reference product.

    To access the full report, please click here

    ASCO addressing the spiralling cost of cancer care

    Published earlier this year, ASCO in Action Brief: Value in Cancer Care targets issues related to cost, quality, and value of cancer care to address the unsustainable rate at which health care costs are growing in the United States. “If the economic costs of healthcare in general, and high-quality cancer care in particular, continue to rise unchecked, it will be less and less affordable for an increasing number of Americans.” While ASCO is examining the overall delivery of care, cancer drugs are a key area of focus because they currently compose eight out of the top ten most expensive drugs covered by Medicare. With new drugs offering incremental improvements in survival, “there is a growing, widespread recognition that high-cost care does not necessarily translate into high-quality care or improved outcomes.”

    Under the leadership of the Value in Cancer Care Task Force, ASCO has launched a new strategic initiative to develop a methodology for determining the relative value of cancer treatment and interventions to help physicians make the best decisions with and for their patients. A key challenge within this initiative is the spiralling costs of new cancer therapies and tests, and ASCO is quite clear in their direction to oncologists, stating that they “have not only a role, but indeed a responsibility to help address and manage the issue of high drug costs on behalf of our patients.”

    “Most troubling to ASCO are the reports that high drug prices are limiting patient access to treatment and challenging patients’ (and their families’) financial stability and security. The overall burden on the national economy translates into enormous strain at the individual level: patients and their families affected by disease often face crippling expenses during what is already one of the most difficult and stressful times in their lives.”

    In fact, medical costs are the leading cause of personal bankruptcy in the United States and the costs of cancer care are a key contributor to this societal problem.

    It is not clear at this time what position ASCO will take on the adoption of biosimilars. What is clear, however, is the need to clearly define the value of medications to provide the most optimal, sustainable care.

    To access the full brief, please click here.

    May 2014   +

    Health Canada does not allow extrapolation to all indications for Remicade® biosimilar

    In January of 2014, only four months after Remicade® received biosimilar approval in the EU, the Canadian authorities granted approval of Remsima™ and Inflectra™ as subsequent entry biologic (SEB) products, the term used in Canada to describe biosimilar products. However, unlike the EU regulators, Health Canada did not allow extrapolation of the data to cover the gastrointestinal (GI) indications of Crohn’s disease and ulcerative colitis and asked for additional data. Celltrion, the manufacturer of Remsima™ and application holder, is known to be conducting additional clinical trials in Crohn’s disease and ulcerative colitis as part of the post approval commitment to EU authorities. Quintiles believes that it is possible that the data from these clinical trials will be used to seek approval for GI indications for Remsima™ and Inflectra™ in Canada in the future.

    For the full press release, please click here.

    France, the first EU country to allow biosimilars substitution

    Effective 1 January 2014, a new law concerning the Social Security budget has adapted provisions that allow the substitution of originators by generics to extend to biosimilar products. Now, pharmacists in France will be allowed to substitute a biosimilar for the prescribed (reference) biological as long as the prescribing physician has not marked the prescription as ‘non-substitutable’.

    If the pharmacist substitutes a biosimilar for the prescribed biological, he/she is required to inform the prescribing physician in addition to writing the name of the dispensed product on the prescription.

    Substitution of a biosimilar is to be allowed only when initiating a course of treatment. If the treatment is then continued and the prescription is renewed, the same (substituted) medicine should be dispensed.

    The law is clear that patients who have already started treatment on a biologic medicine must not have their medicine substituted by a pharmacist.

    France is the first EU country to permit biosimilar substitution. Decisions regarding substitutability in the EU are made at the Member State level. To date, no other EU country has explicitly authorized the substitution of biologicals with biosimilar versions and a number of Member States have actually banned this practice.

    For the full press release, please click here

    Norway to facilitate switch to biosimilars with $3m Remicade® study

    The Norwegian Health Department has committed $3.3m to a switching study from Remicade® to its biosimilar version, in part to help facilitate the use of biosimilars. As a general rule, the EMA does not require a switching study from the branded drug to its biosimilar as part of the approval process in the EU. According to Norwegian authorities, data from this study will help “increase physician and patient confidence” and in the future lead to increased uptake of biosimilars.

    For the full press release, please click here