A biosimilar agent to Remicade, the brand-name and reference form of infliximab, stayed on track to become the second biosimilar drug to enter the U.S. market when the Arthritis Advisory Committee of the Food and Drug Administration voted overwhelmingly in favor of licensure of the biosimilar at a meeting on Feb. 9.
The vote was 21 in favor and 3 against, with no abstentions.
Because of the way the FDA staff worded the question that the Advisory Committee voted on, the panel not only was in favor of approving biosimilar licensure but also recommended that license for six of the seven diverse indications that Remicade currently has: treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, adult and pediatric Crohn’s disease, and adult ulcerative colitis. The panel did not vote on licensing the biosimilar for treatment of pediatric ulcerative colitis because that specific indication for Remicade remains on patent for a few more years.
The broad range of indications for which the Committee recommended approval was notable because the formulation of biosimilar infliximab under review, manufactured by Celltrion and known in the United States as CT-P13, had been clinically studied only in patients with rheumatoid arthritis or ankylosing spondylitis. The other four recommended indications represented extrapolations, based on the totality of biosimilar evidence presented at the meeting by both Celltrion staffers and consultants as well as analyses presented by FDA staff members.
The overall thrust of the extrapolation issue was that if biosimilarity to Remicade was proven by a range of preclinical and clinical testing, and if safety and efficacy similar to Remicade was shown in trials that enrolled only patients with rheumatoid arthritis or ankylosing spondylitis, then the safety and efficacy previously proven for Remicade for the other indications could be reasonably extrapolated to apply to CT-P13 also, even though CT-P13 was never tested on patients with those conditions. This turned out to often be the key issue that panel members grappled with as they decided whether to vote in favor of the question the FDA asked them to address.
“Many of us are uncomfortable with this new pathway” of extrapolation, said panel member Dr. Beth L. Jonas, a rheumatologist at the University of North Carolina at Chapel Hill.
“I feel we’re taking a risk” with the extrapolations, said Dr. Mary E. Maloney, professor of medicine and chief of dermatology at the University of Massachusetts in Worcester. “We have a responsibility to take a risk to provide biosimilars to patients and to reduce their cost” for needed treatments, she said during the Committee’s discussion of their votes.
“Biosimilar is a new concept, but it’s the future of how we will look at drugs,” explained panel member Dr. Wilma Bergfeld, professor of dermatology at the Cleveland Clinic.
CT-P13 is currently marketed in many other countries worldwide under the brand names Remsima or Inflectra.
The FDA’s staff was clearly behind this application. After summarizing the agency’s internal analysis of the data submitted by Celltrion, Dr. Nikolay Nikolov, clinical team leader for the FDA’s Division of Pulmonary, Allergy and Rheumatology Products, concluded that “the totality of evidence provided by the applicant supports a conclusion that CT-P13 is biosimilar to U.S.-licensed Remicade,” and that “scientific justification for extrapolating the clinical data supports a finding of biosimilarity for all indications for which U.S.-licensed Remicade is licensed.” The FDA’s position makes it seem very likely that the agency will accept the Advisory Committee’s vote and grant CT-P13 license for U.S. marketing in the near future.
CT-P13 also received support during the public comment period of the Committee’s deliberations. At that time, Dr. Gideon P. Smith, a dermatologist at Massachusetts General Hospital in Boston spoke on behalf of the American Academy of Dermatology Association. “Biologics are some of the most important recent developments in treating plaque psoriasis, but cost is an important issue. We hope that biosimilars will decrease the cost of this treatment,” Dr. Smith said. “Infliximab is a complex molecule with a complex production process. We are concerned about the safety and efficacy of treatment. The AADA supports approval based on reducing cost and improving patient access. However, we strongly recommend caution through long-term postmarketing surveillance and using registry data to identify issues of immunogenicity, efficacy, and safety that were not seen in the clinical trials.”
The drug also received support from Dr. Angus B. Worthing, who represented the American College of Rheumatology. “Biosimilars may be the only tool to keep prices of biologics within reason,” said Dr. Worthing, a rheumatologist in Washington. But he also stressed that “extrapolation should be done with caution and not routinely granted.”