COMMENTARY

Biosimilar Infliximab: One Step Closer to the Pharmacy?

Jonathan Kay, MD

Disclosures

February 25, 2016

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Hello. I'm Dr Jonathan Kay, professor of medicine and director of clinical research in the division of rheumatology at the University of Massachusetts Medical School and U Mass Memorial Medical Center, both in Worcester. Welcome to my Medscape blog.

On February 9, I attended the US Food and Drug Administration (FDA) Arthritis Advisory Committee hearing on CT-P13, a biosimilar infliximab developed by Celltrion in South Korea. This was a historic occasion—for the first time the FDA considered approving a biosimilar of a large complex biopharmaceutical used to treat inflammatory diseases. Key questions at this meeting were: Would the advisory committee recommend approval of this biosimilar? And, most important, could indications be extrapolated from clinical data generated in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) to patients with diseases for which reference infliximab (Remicade®) is approved but in which the biosimilar had not been studied? These diseases include psoriasis, psoriatic arthritis, Crohn disease, ulcerative colitis, and pediatric Crohn disease. Pediatric ulcerative colitis was not considered because the patent exclusivity for Remicade extends longer in that indication.

The meeting began with an overview of the FDA's biosimilar review process by Janet Woodcock, MD, director of the Center for Drug Evaluation and Research. Then Celltrion presented clinical data showing high similarity in virtually all of the analytical studies between CT-P13 and both United States- and European-sourced Remicade. However, there was lower G0 glycan content in CT-P13 compared with both United States- and European-sourced Remicade, which resulted in lower binding to the Fc-gamma-RIIIa receptor and, as a result, lower antibody-dependent cell-mediated cytotoxicity (ADCC) in certain assays. This difference was only in about 10% of the lots of CT-P13, and the rest fell within the reference range for ADCC. There were several different ADCC assays; some showed very little difference, and others showed a slightly more pronounced difference. However, Celltrion presented data from in vitro assays in which colon cells from patients with Crohn disease had much less ADCC compared with colon cells from healthy donors. This suggests that ADCC may not be such an important mechanism in Crohn disease or other forms of inflammatory bowel disease (IBD).

The clinical data in both AS and RA showed highly similar efficacy, safety, and immunogenicity between CT-P13 and reference infliximab. The lack of data or relative lack of data in IBD was somewhat mitigated by data presented by Peter Lakatos, MD, a gastroenterologist from Budapest, Hungary, who described results from a large postmarketing study of CT-P13 in Hungarian patients with IBD. In this population, as well as in an ongoing phase 4 study in patients with Crohn disease, there was similar immunogenicity between CT-P13 and reference infliximab.

Next there were presentations from members of the public, some of whom expressed concern or skepticism about the efficacy and safety of a biosimilar. Sarah Buchanan, director of advocacy for the Crohn's & Colitis Foundation of America, made a very articulate plea for the FDA to consider approval of this biosimilar infliximab because it would introduce price competition into the market. She said that patients with Crohn disease and other forms of colitis are willing to accept the slight uncertainty about the long-term efficacy and safety of a biosimilar if it allows more patients greater access to this very effective therapy.

After the public comment, the FDA advisory committee discussed the data that had been presented and ultimately voted 21-3 in favor of approving this biosimilar infliximab with extrapolation to all indications. In this regard, the FDA differs from Health Canada, where CT-P13 was approved for RA, AS, psoriasis, and psoriatic arthritis but not for IBD. Thus, the FDA followed the lead of the European Medicines Agency in extrapolating indications for CT-P13 to all of those indications for which the reference product, Remicade, has been approved. This hearing marks the first of a number of upcoming hearings of biosimilar candidates for other tumor necrosis factor inhibitors in treating patients with inflammatory diseases.

I hope you found this topic interesting and the area of biosimilars as exciting as I do. I look forward to seeing you again on Medscape. Thank you very much. I'm Dr Jonathan Kay.

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