Opinion: Embrace the Era of Next-Generation Biologics

In the United States, although the first biosimilar obtained approval from the FDA in 2015, these drugs have been slow to gain support and implementation in clinical practice. Biosimilars of several anti–tumor necrosis factor (TNF) agents have been approved. Currently, 3 infliximab biosimilars are available for the treatment of inflammatory bowel disease (IBD).

Although the infliximab biosimilars are approved for the same indications as the reference infliximab, research shows that many gastroenterologists are still reluctant to use infliximab biosimilars for Crohn disease (CD) or ulcerative colitis (UC).¹ Perhaps the most common reason is that insurance coverage for biosimilars has not been widely available, making it difficult to prescribe or switch them. However, even when biosimilars are covered, providers may still hesitate to use these agents. They may not know about biosimilars or their safety and efficacy, or they may lack clinical experience in using them.

What Is a Biosimilar?

A biosimilar is a biological product that is highly similar to and has no clinically meaningful difference from an existing FDA-approved reference product.² In order to understand biosimilars, one must understand the “totality of evidence” approach, which forms the foundation of biosimilar development programs. In the early stages of biosimilar development, extensive, rigorous studies are conducted to demonstrate structural and functional similarity between the reference biologic and biosimilar. Once this similarity is established, clinical studies are conducted in one or more sensitive populations to “confirm” equivalent efficacy and safety.³ Biosimilars undergo a thorough regulatory review process, and biosimilars approved by the FDA can be regarded as safe and effective for use based on robust scientific evidence.

Are Biosimilars Safe for Patients With IBD?

Biosimilars were introduced earlier in Europe than in the United States, and they have been used without major safety issues for more than 10 years. Several real-world studies conducted in Europe demonstrate the safety of switching from reference infliximab to biosimilars, or from one biosimilar to another biosimilar in the IBD population. One long-term observational, prospective cohort study conducted in Germany showed that switching 148 patients with IBD (96 with CD, 52 with UC) from reference infliximab to a biosimilar did not lead to any increase in disease activity.⁴ In another prospective, single-center observational study conducted with 221 patients (179 with CD, 42 with UC), there was no adverse effect on IBD control or drug levels after the first or second switch.⁵

In the United States, real-world evidence on biosimilars for patients with IBD has been rather limited, but the data are growing with increasing use of biosimilars. Recently, at the American College of Gastroenterology (ACG) 2020 Virtual Annual Scientific Meeting, held from October 26 to 28, 2020, real-world data on US veteran patients with IBD revealed that a single switch from reference to biosimilar infliximab, or a double switch from the reference product to a biosimilar to another biosimilar, did not lead to any significant safety issues.⁶ Patients who were stable on the original infliximab medication for at least 3 months were eligible for the study, and they continued to remain stable after switching.

In another real-world study conducted by Cleveland Clinic, patients were randomized to switch to infliximab biosimilar or continue on reference infliximab. The study demonstrated that there was no significant difference in the use of corticosteroid taper, maintenance of remission rates, fecal calprotectin levels, infliximab concentrations, or antibody levels between these 2 groups.⁷ Since data are limited on multiple switching of biosimilars to reference product or from one biosimilar to another, this information would be important for the FDA to authorize interchangeable status for a biosimilar, which would allow pharmacists to independently substitute biosimilars when dispensing. No biosimilars have that designation to date.

How Does COVID-19 Affect the Use of Biosimilars?

Use of biosimilars can help drive down overall health care costs. Especially now, as the United States continues to battle the coronavirus disease 2019 (COVID-19) pandemic, there will be an increasing burden on the health care system to finance budgets and find savings to ease some of that burden for patients, providers, payers, and employers. Development of new vaccines and treatments for COVID-19 requires billions of dollars of funding from both private and public sources. And trillions of dollars are needed to support hospitals and health care providers for costs and expenses associated with COVID-19. This is an enormous strain on the health care budget, but there is room to drive down the cost of existing medicines through wider adoption of biosimilars.

Also, as patents expire on some biologic molecules in the next few years, there will be more biosimilars available for a wider spectrum of therapies in the market. For adalimumab, 6 biosimilars have FDA approval to enter the US market in 2023 and more are anticipated.⁸ Will rheumatologists, gastroenterologists, and dermatologists in the United States be ready to use biosimilars by then?

It will be interesting to see how biosimilars change the daily practice of IBD treatment in the coming years. With approximately 3 million Americans living with IBD, and the burden and prevalence of IBD continuing to increase,⁹ it’s time to embrace the change and think with a holistic point of view. Biosimilars, as treatment options with lower cost than reference products but with the same efficacy and safety, can be the optimal solution to maintain quality care for patients while reducing the cost burden on the health care system in the United States.

References

1. Park SH, Park JC, Lukas M, Kolar M, Loftus EV. Biosimilars: concept, current status, and future perspectives in inflammatory bowel diseases. Intest Res. 2020;18(1):34-44. doi:10.5217/ir.2019.09147

2. FDA. Biosimilar and interchangeable products. Updated October 23, 2017. Accessed October 2020. https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products

3. FDA. Biosimilar development, review, and approval. Updated October 20, 2017. Accessed October 2020. https://www.fda.gov/drugs/biosimilars/biosimilar-development-review-and-approval

4. Fischer S, Mesfin S, Klenske E, et al. P548 Efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in inflammatory bowel disease patients: A long-term observational, prospective cohort study. J Crohns Colitis. 2020;14(Suppl 1):S466-S467. doi:10.1093/ecco-jcc/jjz203.676

5. Luber R, O’Neill R, Singh S, Arkir Z, Irving P. P485 Switching infliximab biosimilar: no adverse impact on inflammatory bowel disease control or drug levels with the first or second switch. J Crohns Colitis. 2020;14(Supplement_1):S426-S427. doi:10.1093/ecco-jcc/jjz203.614

6. Pernes T, Patel M, Khan N. The safety of switching from originator infliximab or CT-P13 to SB2 among a nationwide cohort of inflammatory bowel disease patients. Presented at: ACG 2020 Virtual; October 23-28, 2020. Poster 1597.

7. Padival R, Heis F, Lee JA, et al. Real world comparison of originator infliximab versus the biosimilar infliximab-abda in the treatment of inflammatory bowel disease. Presented at: ACG 2020 Virtual; October 23-28, 2020. Poster 1625.

8. Davio K. FDA approves Pfizer’s adalimumab biosimilar, Abrilada. The Center for Biosimilars^®. Published November 16, 2019. Accessed October 2020. https://www.centerforbiosimilars.com/view/fda-approves-pfizers-adalimumab-biosimilar-abrilada

9. Centers for Disease Control and Prevention. Inflammatory Bowel Disease Data and Statistics. Updated August 11, 2020. Accessed October 2020. https://www.cdc.gov/ibd/data-statistics.htm