Challenges, Obstacles, and Future Directions for Anti-TNF Biosimilars in IBD

A review article on tumor necrosis factor (TNF)-α inhibitors in inflammatory bowel disease (IBD) outlined current use of anti-TNF originators and biosimilars, their efficacy and safety, the benefits and challenges of biosimilars, and the future of biosimilars in IBD.

IBD is an umbrella term for Crohn disease (CD) and ulcerative colitis (UC), immune-mediated inflammatory diseases of the gastrointestinal tract with significant negative impact on quality of life. The authors noted that the risk of colorectal cancers in patients with UC is twice that of the general population, and that high hospitalization and surgery rates increase costs for patients with IBD.

The reviewers cited estimates of health care costs for CD and UC in the US, Europe, and China. Major drivers of health care costs were previously hospitalization and surgery; however, they said, with the introduction of biologics, drugs have accounted for the majority of costs. Currently, anti-TNF therapies account for 64% and 31% of the total costs in CD and UC.

The most important benefit of biosimilars, the authors said, is cost savings. They cited data showing biologics account for about three-quarters of prescription drug spending under Medicare Part B, and that the cumulative cost savings attributable to biosimilars in the US from 2015 to 2022 was estimated at $23.6 billion and expected to increase to $130 billion in 2025. They also noted the use of biosimilars increases patient access to biologic therapies.

The reviewers included a brief discussion of each infliximab and adalimumab biosimilar and its approval status. The infliximab biosimilar CT-P13 (Remsima/Inflectra; Celltrion) was the first infliximab biosimilar to be approved by the European Medicines Agency (EMA) in September 2013 and was the first monoclonal antibody biosimilar approved by the agency. CT-P13 was approved by the FDA for use in IBD in 2016. The first adalimumab biosimilar approved by the EMA (in 2017) and FDA (in 2016) was ABP 501 (Amjevita/Amgevita). Several additional anti-TNF biosimilars have been approved for IBD since, such as infliximabs SB2 (Flixabi) and GP1111 (Zessly) and adalimumabs SB5 (Imraldi),BI 695501 (Cyltezo), GP 2017 (Halimatoz), and MSB11022 (Idacio), “significantly expanding the treatment options for patients.”

Challenges and Obstacles for Biosimilars

The “major threat” to market entry of biosimilars, the authors wrote, are “the extensive patent protections and complex patent litigation on originators.” Data cited by the authors of the review suggest that Germany overall has the highest market share for biosimilars, followed by the US and Switzerland. The market share of biosimilars varies across countries, which the authors said can be partly explained by different policies for market entry, reimbursement, and drug price negotiation in different countries.

For example, reimbursement policies in the US incentivize pharmacy benefit managers to choose higher-priced originators over biosimilars to receive higher rebates. In China, lack of insurance coverage for some biosimilars hinders uptake, and “more incentive programs are needed in China,” the reviewers wrote.

Another major obstacle is interchangeability. Standards for interchangeability in the US are “rigorous,” and the number of interchangeable biosimilars remains small. Pharmacy-level substitution of biosimilars for reference products also varies between countries, “suggesting a need to analyze biosimilar issues based on national conditions.”

Finally, “prescription inertia” on the part of physicians and acceptance by patients are also obstacles to increasing market share of biosimilars. In part, the authors said, this could be due to most clinical trials for biosimilar approval conducted in diseases other than IBD, resulting in concerns about efficacy and safety in IBD.

The Future of Biosimilars in IBD

The reviewers closed by saying that biosimilars play a key role in IBD treatment. To address concerns from physicians and patients, they said there is a “pressing need” for more studies to confirm effectiveness and safety of anti-TNF biosimilars in IBD, and “with an increasing number of alternative biosimilars for IBD patients, more efforts should also be put into the investigation of efficacy and immunogenicity profiles of multiple successive switches between originators and biosimilars.” Analyses of cost-effectiveness are also warranted, they added. Finally, the authors discussed anti-TNF biosimilars in the context of precision medicine, saying that individualized and precise therapeutic plans for each patient are “highly crucial.” They suggested establishing predictive models of patient response to anti-TNF biosimilars and to switching and analyzing biomarkers to predict therapeutic response will be important to IBD care in the future.

Reference

Zeng Z, Lin H, Jiang M, Yuan J, Li X, Jia Y, Yang L, Zhang H. Anti-TNFα in inflammatory bowel disease: from originators to biosimilars. Front Pharmacol. 2024;15:1424606. doi:10.3389/fphar.2024.1424606