2016 in Review

QuintilesIMS experts reflect on the growing confidence in biosimilars worldwide – and the barriers that still remain

2016 marks the tenth anniversary of the launch of the first biosimilar in Europe and Medicines for Europe claims:

  • Across Europe, nearly 90% of doctors now know what biosimilar medicines are and nearly 60% have already prescribed them.1
  • Since the first biosimilar medicine was launched in 2006, European Union (EU)-approved biosimilars have generated more than 400 million patient days of positive clinical experience.1
  • Between 2006 and 2014, biosimilar medicines have increased patient access by 44% overall within in the EU-5 countries.1 

As of October 2016, the European Medicines Agency (EMA) has approved 23 biosimilars and the United States (US) Food and Drug Administration (FDA) – which took longer to formulate its guidance for biosimilar development – has just approved its fourth. Many other highly regulated markets – such as Canada, Australia, Japan, and South Korea – are demonstrating a similar commitment to introducing biosimilars, recognizing the significant benefits of making important biologic therapies more affordable and thereby increasing patient access within their populations. 

Only a few years ago, when biosimilars were still relatively unfamiliar, many prescribers and other stakeholders were concerned about whether these products would prove to be as effective and safe as originator biologics and, in particular, about the possibility of greater immunogenicity. Even those who were more convinced – especially in the light of the rigorous regulatory requirements – were doubtful about the idea of switching between an originator and a biosimilar in individual patients. Most announcements from academic societies advocated caution.

Today the picture is very different. Confidence among clinicians – and the societies who represent them – has increased significantly. This growing confidence is underpinned by accumulating clinical experience with licensed biosimilars worldwide, and a growing number of publications confirming the clinical similarity of approved biosimilars with their originators. Reassuring data from switching studies has also been forthcoming and most importantly – there have been no negative reports regarding biosimilar usage. 

What notable reports have been published in 2016?   +

  • A real-world prospective study in over 1,400 patients with chemotherapy-induced febrile neutropenia added to growing evidence for the clinical similarity of biosimilar filgrastim compared with the originator.2

  • A major systematic review of 19 studies, published in the Annals of Medicine, reported that TNF-α inhibitor biosimilars for the treatment of rheumatoid arthritis and other autoimmune diseases appear to be as effective and safe as their branded equivalents.3

  • At the 2016 annual EULAR (European League Against Rheumatism) congress, data were presented on patients transitioned from originators etanercept (n=254) and infliximab (n=396) to their biosimilar counterparts. In both cases there were no treatment-emergent safety or immunogenicity issues, and efficacy was sustained for up to 2 years.4

  • Delegates at the 2016 European Crohn’s and Colitis Organisation (ECCO) congress heard that ten real-world studies involving nearly 600 patients with inflammatory bowel disease all showed similar efficacy and safety following a switch to biosimilar infliximab from the originator.5

What are the signs that receptivity to biosimilars is increasing?   +

FDA approves four biosimilars

The US FDA – which has so far been seen as the most cautious and conservative regulatory body – has now approved four biosimilars (filgrastim, infliximab, etanercept, and adalimumab) and has in most cases also approved extrapolation of the data submitted to all other licensed indications of the relevant originator. The agency has also increased its internal resources to handle the volume of biosimilar applications it is now receiving.

Academic medical societies endorse biosimilar use

  • The American College of Rheumatologists, who describe biologics as a “lifeline,” which “many of our patients struggle to afford,” applauded the FDA approval of biosimilar infliximab.
  • The British Society of Gastroenterologists was equally vocal in its support for biosimilar versions of infliximab, based on clinical experience in Europe.
  • EULAR has published a position paper on how best to explain biosimilars to patients.
  • The American Society for Clinical Oncology (ASCO) has endorsed the use of biosimilar filgrastim (the first FDA-approved biosimilar) and the US National Comprehensive Cancer Network (NCCN) has publicly encouraged US oncologists to regard biosimilars as a useful alternative to expensive originators.
  • The American College of Physicians (ACP) has highlighted the need to remove obstacles and “clear the way” for biosimilar uptake as part of its recommendations on ways to stem the rising cost of US prescription drugs.

More national bodies dedicated to biosimilars

Many countries have now re-branded their national generics associations to include biosimilars or have set up dedicated biosimilars committees and panels. 2016 saw the launch of the British Biosimilars Association and a similar organization in Japan.

More biopharma companies plan to develop biosimilars

  • A 2016 survey revealed that over 60% of companies currently involved in developing and marketing innovator biologics (including large multinationals) also have plans to invest in biosimilars – or are already doing so. The findings show that the development and commercialization of biosimilars and innovator biologics no longer fall within two separate “camps”.6
  • Trade bodies that represent pharmaceutical companies are recognizing the changing landscape. 
    • Teva Pharmaceuticals, one of the world’s largest generic drug makers, recently became a member of the Pharmaceutical Research and Manufacturers of America (PhRMA), which had previously been a staunch defender of brand-name companies.
    • The International Council for Harmonisation (ICH) – traditionally representing companies involved with innovative drugs – has announced that the International Generic and Biosimilars Medicines Association (IGBA) could join as an Assembly Member. 

Payers drop coverage of originator biologics in favor of biosimilars

  • US: CVS Heath Corp, whose Caremark unit administers drug benefit plans for employers and insurers, will drop coverage of branded filgrastim and insulin glargine and only cover licensed biosimilar versions as of January 2017. United Health Group made the same announcement shortly afterwards.
  • France: The central purchasing agency for the Assistance Publique – Hôpitaux de Paris, which cares for nearly 25% of the French population, opted for a biosimilar version of infliximab over the originator after negotiating a 45% discount with the manufacturer.
  • UK: The National Institute for Health and Care Excellence (NICE), which decides which medicines will be funded by the National Health Service (NHS), has recommended use of licensed biosimilars as first-choice agents in several indications and no longer differentiates between originators and licensed biosimilars in its clinical guidelines.
What barriers still remain for the commercialization and uptake of biosimilars?   +

Innovator manufacturers are utilizing defensive tactics

Faced with biosimilar competition, the manufacturers of top-selling originators are finding new ways to enhance the competitiveness of their products beyond price cutting: 

  • New formulations designed to reduce injection pain, doses, and the number of injections.
  • Subcutaneous formulations with advantages over intravenous infusions in terms of delivery times.
  • Applications for new indications, which will come with brand new patents.
  • Development of second-generation products that can be shown to outperform older biologics in head-to-head studies.

Patent lawsuits delay the launch of biosimilars

The first FDA-approved biosimilar, ZarxioTM, was licensed in March 2015 but did not reach the market until September of that year due to litigation by the originator manufacturer, who claimed its patents had been infringed. Similar lawsuits are highly likely to delay the launch of the other FDA-approved biosimilars, despite the “friendly” exchange of patent information that is supposed to happen before FDA submission. Some originator products have numerous patents related not only to the active substance but also to the formulation, method of manufacture, and means of delivery, meaning that lawsuits can be complex and lengthy to resolve.

Interchangeability is yet to be fully resolved in the US

For a patient already stabilized on an originator biologic, the acceptability of biosimilar substitution by a pharmacist (without necessarily consulting the prescriber) is naturally seen as an advantage by biosimilar manufacturers. The US FDA intends to grant a designation of interchangeability as an additional approval step, distinct from approving a product as a biosimilar. Only interchangeable biosimilars will be eligible for pharmacist substitution – and even then, individual States have the power to prevent or sanction this. However, the FDA has yet to confirm the criteria for gaining interchangeability approval.

Some governments discourage biosimilars through price controls

In Spain and in the Republic of Ireland, originator manufacturers are obliged to automatically discount their prices upon patent expiration. This mandate reduces the financial incentive to introduce biosimilars into these markets.

Understanding and education still patchy among prescribers

In 2016, SERMO, the leading global social media network exclusively for doctors, announced the results of a biosimilars poll involving 3,849 clinicians from 28 countries worldwide. Encouragingly, it showed that 90% of those polled were receptive to prescribing biosimilars. However, of these, nearly half said they would need more educational information on biosimilars before prescribing them.7

Patient awareness of biosimilars is still low

An international survey conducted to understand the levels of awareness of biosimilars among patients, caregivers, and the general population in the US and EU (n=3,198) 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 is only 6%.8 

Clearly, the barriers to optimal biosimilar uptake remain fairly formidable. However, as positive clinical experience with biosimilars accumulates globally, and the advantages of reduced expenditure and greater patient access become more evident, the gathering momentum behind the biosimilars revolution seems unlikely to abate.
References   +

  1. Biosimilar News, 28 April 2016. 10 Years of biosimilar medicines in Europe: transforming healthcare. Accessed 29 December 2016.

  2. Gascón P, Aapro M, Ludwig H et al. Treatment patterns and outcomes in the porphylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study). Support Care Cancer (2016) 24:911925.

  3. Rheumatoid Arthritis News, 5 August 2016. Generic biologic drugs appear comparable to brand-name counterparts, according to review. Accessed 29 December 2016.

  4. Biogen, 9 June 2016. New data presented at the Annual European Congress of Rheumatology (EULAR 2016) demonstrate safety and efficacy of Biogen’s anti-TNF biosimilars portfolio. Accessed 29 December 2016.

  5. Business Wire, 18 March 2016. Celltrion Healthcare: Switching to Remsima® (infliximab) from originator has no negative effect on safety or efficacy in 10 real-world studies. Accessed 29 December 2016.

  6. EIN News, 17 May 2016. Two-thirds of biopharma sponsors surveyed currently sell or plan to sell biosimilar products. Accessed 29 December 2016.

  7. Business Wire, 8 June 2016. Biosimilars: Safe and effective? Global doctors split on trust. Accessed 29 December 2016.

  8. Dovepress, 26 May 2016. Patient attitudes and understanding about biosimilars: an international cross-sectional survey. Accessed 29 December 2016.