Encouraging competition in the biologics market by increasing adoption of biosimilars is “the most promising approach to increase access to much-needed drugs,” according to the authors of a review article in Seminars in Arthritis and Rheumatism, which discussed recent developments and the future outlook for anti-inflammatory biologic therapy, including biosimilar availability in the United States and European Union.
The reviewers said there are more than 560 biosimilars in development worldwide. Biosimilars are currently available for chronic immune-mediated inflammatory diseases within rheumatology, gastroenterology, and dermatology. These include tumor necrosis factor alpha inhibitors, such as adalimumab, etanercept, and infliximab; and rituximab, an antibody to a surface antigen on B cells. These biosimilars have been approved for all indications of the reference products.
Biosimilars in the US vs EU
The reviewers pointed out marked differences between the United States and European Union in biosimilar use, with biosimilars “widely adopted” in Europe. They said this may be due in part to the earlier introduction of biosimilars in the European Union.
The first anti-inflammatory biosimilar was launched in 2006 in the European Union. Since then, the European Medicines Agency has approved more than 60 biosimilars. The US FDA approved its first biosimilar in 2015. Since then, 33 biosimilars have been approved by FDA and 11 launched.
The authors said that hospitals in Europe have largely adopted biosimilars into their formularies, leading to “steep price reductions of 10% to 35% or more.” In contrast, patent protections have delayed US hospital formulary changes until 2029 for etanercept and 2023 for adalimumab. They added that many US states do not allow pharmacists to substitute a biosimilar without the knowledge of the prescribing physician, a practice more commonly allowed in European countries.
The reviewers cited additional reasons for slow biosimilar adoption in the United States, including patent disputes and other attempts by reference product manufacturers to delay biosimilars from entering the market, poor understanding of biosimilars by many providers and patients, and insufficient cost savings associated with switching to biosimilars to promote wider adoption, in particular for infliximab. The authors view education on biosimilars as “paramount” to increasing biosimilar adoption. Achieving cost savings in the US similar to those in the European Union “may not be possible unless the US pharmaceutical market undergoes reform,” they added.
Competition, Innovation, and the Future of Anti-Inflammatory Biosimilars
The reviewers emphasized the importance of competition in the biologics market, both among biosimilars and between biosimilars and originators, which “drives technical innovation.” Subcutaneous dosing for infliximab is “a key example” of this innovation, they said, in addition to “numerous improvements in the understanding of pharmacokinetics and algorithms for best individual use.”
The authors discussed changes in the biosimilar regulatory landscape, such as the FDA’s Biosimilars Action Plan, published in 2018 to aid the development of the biosimilars market to increase competition. In the European Union, the reviewers expected a “relaxation” in the requirement for comparative clinical efficacy trials for biosimilar approval. They wrote that the value of the clinical efficacy trial has been “increasingly questioned,” and the consensus is shifting toward the idea that analytical tools and a comparative pharmacokinetic trial can largely predict clinical comparability.
They said this shift has begun in the United Kingdom, as the Medicines and Healthcare Products Regulatory Agency published guidance in May 2021 for a streamlined biosimilar regulatory pathway, which “in essence…removed the requirement for a comparative phase 3 efficacy trial in most cases where a well-argued justification can be provided.”
Some biosimilars approved by extrapolation have undergone additional studies in indications of interest, allowing for increased confidence in these biosimilars by patients, payers, and providers. For example, the infliximab biosimilar CT-P13, whose approval was based on a clinical study in rheumatoid arthritis has now been evaluated in inflammatory bowel disease. With these studies and more real-world evidence, the authors expect “physicians will become confident not only in initiating patients to biosimilars but also in switching patients to and between them.”
To create a sustainable biosimilar market, the reviewers recommend policies designed to eliminate barriers to biosimilar market entry, and increase physician and patient adoption of biosimilars, saying “policies that would provide affordable and accessible therapeutics to patients should be encouraged, despite the seemingly little political appetite to implement them.”
The authors concluded that biosimilars have already impacted clinical outcomes in rheumatology, gastroenterology, and dermatology, and affordable access to biologics via biosimilars will allow biologics to be used earlier in the course of disease, leading to better long-term outcomes.
Schreiber S, Puig L, Gonçalves J, Mease PJ, Panaccione R, Emery P. Critical appraisal and future outlook on anti-inflammatory biosimilar use in chronic immune-mediated inflammatory diseases. Semin Arthritis Rheum. 2022;55:152023. doi:10.1016/j.semarthrit.2022.152023.