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In a new scenario for the biosimilar industry, Celltrion is investigating a subcutaneous formulation of its biosimilar of infliximab, given biweekly. This is significant because the originator, Remicade®, is only available as an intravenous infusion. Findings from Celltrion’s research were announced at the Annual Meeting of the European Congress of Rheumatology in June (2018). The researchers studied 48 patients with rheumatoid arthritis (RA) and compared clinical outcomes achieved by three different dosages of the subcutaneous formulation with those of the original infusion. At 30 weeks follow-up, no differences in efficacy were reported in any subgroup. Some hypersensitivity and injection site reactions were observed with the subcutaneous formulation, but the risk of antidrug antibodies appeared to be lower than that with the infusion. Currently, infliximab treatment requires a lengthy office visit for each infusion (every 8 weeks in the maintenance phase), which is one of the key limiting factors to its use. A self-injectable formulation should result in lower administration costs and greater patient convenience. Additional data in both RA and Crohn’s disease is forthcoming later this year. Although it is not yet clear what type of data regulators such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) would require for approval of a new formulation of a biosimilar, it is anticipated that the application would be viewed in the same way as a new route of administration for any approved product, which would focus chiefly on pharmacokinetic and pharmacology data. However, Celltrion seems to be covering all its bases.
The question of how appropriate it is to switch patients stabilized on an originator biologic to a biosimilar has been the subject of extensive debate, especially in patients with inflammatory bowel disease (IBD). A newly published systematic review sought to evaluate whether patients with IBD can safely be switched from the originator infliximab (Remicade®) to CT-P13 (marketed as Inflectra® and Remsima®). The researchers identified 24 studies including a total of 1326 patients with IBD, which evaluated switches between Remicade® and the biosimilar. Among these patients, disease control (defined as no evidence of disease worsening after a switch) was confirmed in 1163 patients (weighted mean [WM], 88%; 95% CI, 86–89%). When only studies that included a follow-up from 4 to 8 months post-switch were included, the WM rose to 90% (95% CI, 89–92%). No differences in adverse events (AEs) were reported after switching versus before switching, and no new immunogenicity signals arose, although the data on multiple switching is currently limited. “The risks of switching to biosimilars seem to be theoretical and not supported by the real-world experience so far,” write the authors. They add that, in accordance with the European Crohn’s and Colitis Organisation’s position, a switch to the biosimilar is acceptable if the patient’s disease is well controlled on the originator. The decision to switch should be left in the hands of the treating physician, and physicians who do decide to switch should take an active role in educating the patient about the rationale for the change. Jason Schairer, MD, a gastroenterologist practicing in the Henry Ford Health System in Michigan, USA, has reported that patients in his practice who have switched to a biosimilar have not experienced any clinical differences in their treatment thus far, even though some have had to switch their therapy back and forth multiple times.
A key topic at this year’s EULAR (European League Against Rheumatism) Congress, held from June 13–16, 2018, in Amsterdam, the Netherlands, was the patient experience when switching to biosimilars from originators. Researchers from the University of Sydney, Monash Health, and Monash University in Australia, who conducted a survey among 127 patients with rheumatoid arthritis (RA), reported that 75% were receptive to the idea of switching to a biosimilar medicine if their physician recommended it. In addition, researchers from the Amsterdam Rheumatology and Immunology Center in the Netherlands, presented data from 46 patients with RA who were switched to biosimilar infliximab. The patients were first informed by letter about the switch and then contacted by a nurse or pharmacist who answered questions and gained the patients’ consent to switch. On the day of the switch, patients responded to a questionnaire that asked them to evaluate the information provision process. No-one reported that the information was insufficient for their needs.
An association between health literacy and patients’ responses to switching has also been demonstrated. The data were derived from a cohort of 290 Norwegian patients who had undergone a switch to a biosimilar. Patients responded to several questionnaires administered via a web survey, which also collected demographic information and measured health literacy using a multidimensional validated questionnaire. The investigators used three domains covering: (1) patients’ ability to actively engage with healthcare providers; (2) ability to find good health information; and (3) ability to understand health information well enough to know what to do. The authors found that self-assessed good health literacy was strongly associated with a higher probability of being satisfied with the switch.
The International Generic and Biosimilar Medicines Association (IGBA) has been elected as a Management Committee Member of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). According to its mission statement, the ICH works to achieve “greater harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner.” The IGBA joined the ICH in June 2016 as a General Assembly member. Its newly elected role on the management committee “reflects the recognition of values and expertise which the generic and biosimilar pharmaceutical industries can bring to the scientific discussion at the ICH,” the IGBA said in a statement.
In an unusual development, the US Food and Drug Administration (FDA) has withdrawn a draft guidance intended to provide advice for biosimilar sponsors regarding the determination of similarity between a biosimilar and its originator, following concerns about its impact on the biosimilar development process. The original draft guidance, “Statistical Approaches to Evaluate Analytical Similarity,” issued in September 2017, raised public concerns about its impact on the cost and efficiency of biosimilar development. In particular, comments submitted to the FDA questioned the number of lots of the originator product that biosimilar developers were required to sample, as well as the statistical methods for this evaluation. The FDA added that it believes addressing these issues will help the organization promote a more efficient pathway for biosimilar development. “Biosimilars foster competition and can lower the cost of biologic treatments for patients, yet the market for these products is not advancing as quickly as I hoped,” Commissioner Scott Gottlieb said in a press release. “I believe that the FDA can do more to support the development of biosimilars, as well as promote their market acceptance.” In the statement, the FDA said it plans to issue draft guidance that will reflect state-of-the-art analytical techniques and will aim to address the challenges faced by biosimilar sponsors in designing studies. The guidance will also provide “appropriate flexibility” for sponsors, with the goal of spurring efficient biosimilar development “without compromising the agency’s rigorous scientific standards for evaluating marketing applications”.
The American College of Rheumatology (ACR) has released a new position statement on pharmacovigilance emphasizing the need for the continued monitoring of new drugs – including biosimilars – once they are introduced to the market. It states that tracking information about new biosimilars is particularly crucial as greater numbers of these products continue to receive approval for treatment of rheumatic diseases. The ACR advocates for lot numbers to be used for tracking purposes, in addition to the US Food and Drug Administration’s (FDA) naming guidance, providing the most detailed drug information available.
The European Specialist Nurses Organisation (ESNO) has released a detailed guidance document, which advises nurses how best to support patients undergoing a switch to a biosimilar. “Switching between similar biological medicines needs good management. Nurses play a crucial role in communicating with patients and providing support and reassurance, before, during, and after a switch,” said Ber Oomen, Executive Director at ESNO. Specifically, the guidance contains talking points around the rationale for using biosimilars, how to address frequently asked questions from patients, and how to ensure pharmacovigilance is implemented. It cites numerous case studies and real-world data that reinforce the safety and efficacy of biosimilars and includes flow charts that describe how the switch, follow-up, and support process will unfold. It stresses that using positive language is important to help give patients confidence, and urges nurses and other healthcare professionals to adopt a consistent explanation of biosimilars to avoid patient confusion. Currently written in English, the guide is soon to be translated into 23 European languages.
The UK has once again been chosen as the first launch market of a new biosimilar – this time Mylan’s biosimilar of the Sanofi blockbuster Lantus® (insulin glargine). The fertile UK landscape is proving an alluring springboard for biosimilars, as the country’s National Health Service (NHS) has shown high receptivity and proactivity in adopting what is sees as “best value” versions of proven biologics. Mylan believes that early proof of high savings for the NHS drugs bill will motivate other countries that have so far been more resistant to creating a positive environment for biosimilars. The number of people with diabetes in Europe is expected to grow from 58 million today to 67 million by 2045, according to the International Diabetes Federation. The need for new drugs follows that trajectory with a report from analysts Research and Markets predicting the insulin market will continue to grow at an annual rate of just above 6%. Insulin biosimilars could create very significant savings in this space.