The future of anti-inflammatory biosimilars

According to the authors of a review article in Seminars on arthritis and rheumatism, who discussed recent developments and future prospects for anti-inflammatory biologic therapy, including the availability of biosimilars in the United States and the European Union.

Reviewers said there are more than 560 biosimilars in development worldwide. Biosimilars are currently available for chronic immune-mediated inflammatory diseases in rheumatology, gastroenterology and dermatology. These include tumor necrosis factor alpha inhibitors, such as adalimumab, etanercept, and infliximab; and rituximab, an antibody directed against a surface antigen on B cells. These biosimilars have been approved for all indications of the reference products.

Biosimilars in US vs EU

The reviewers pointed to stark differences between the United States and the European Union in the use of biosimilars, with biosimilars being “widely adopted” in Europe. They said this could be partly due to the earlier introduction of biosimilars into 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 the FDA and 11 launched.

The authors said European hospitals have widely adopted biosimilars in their formularies, resulting in “significant 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.

Reviewers cited additional reasons for the slow uptake of biosimilars in the United States, including patent litigation and other attempts by reference product manufacturers to delay biosimilar entry to market, poor understanding of biosimilars by many providers and patients, and insufficient cost savings associated with switching to biosimilars to drive wider adoption, particularly for infliximab. The authors consider biosimilar education to be “key” to increasing biosimilar uptake. Achieving cost savings in the United States similar to those in the European Union “may not be possible unless the US pharmaceutical market is reformed,” they added.

Competition, innovation and the future of anti-inflammatory biosimilars

The reviewers highlighted the importance of competition in the biologics market, both between biosimilars and between biosimilars and originators, which “drives technical innovation”. The subcutaneous infliximab assay is “a key example” of this innovation, they said, in addition to “many improvements in understanding pharmacokinetics and algorithms for better individual use.”

The authors discussed changes in the biosimilars regulatory landscape, such as the FDA’s Biosimilars Action Plan, released in 2018 to help develop the biosimilars market to increase competition. In the European Union, reviewers expected a “relaxation” of the requirement for comparative clinical efficacy trials for approval of biosimilars. They wrote that the value of the clinical efficacy trial has been “increasingly questioned” and the consensus is shifting towards the idea that analytical tools and a comparative pharmacokinetic trial can broadly predict clinical comparability. .

They said this shift started in the UK, as the Medicines and Healthcare Products Regulatory Agency issued guidance in May 2021 for a simplified regulatory pathway for biosimilars, 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 been further studied 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, is now being evaluated in inflammatory bowel disease. With these studies and more concrete evidence, the authors expect “physicians to become confident not only in initiating patients to biosimilars, but also in transitioning patients to and between them.”

To create a sustainable biosimilar market, the reviewers recommend policies designed to remove barriers to biosimilar market entry and increase uptake of biosimilars by physicians and patients, saying that “policies that would provide affordable treatments and accessible to patients should be encouraged, despite the lack of political will to implement them.

The authors concluded that biosimilars have already had an impact on clinical outcomes in rheumatology, gastroenterology and dermatology, and that affordable access to biologics via biosimilars will allow biologics to be used earlier in the lifespan. course of the disease, leading to better long-term outcomes.

Reference

Schreiber S, Puig L, Gonçalves J, Mease PJ, Panaccione R, Emery P. Critical appraisal and future perspectives on the use of anti-inflammatory biosimilars in chronic immune-mediated inflammatory diseases. Semin Arthritis Rheum. 2022;55:152023. doi:10.1016/j.semarthrit.2022.152023.