FDA Advisers Back Infliximab Biosimilar CT-P13

Alicia Ault

February 10, 2016

UPDATED ― Editor's note: This story was updated on November 7, 2016, to clarify statements by Dr Christl of the FDA. The agency does not comment on potential indications for a drug before approval. // SILVER SPRING, Maryland — The US Food and Drug Administration's (FDA's) Arthritis Drugs Advisory Committee gave its backing to CT-P13, a drug that would be the first biosimilar monoclonal antibody approved in the United States.

The committee voted 21–3 that CT-P13 is "highly similar" to the reference product, Janssen Biotech's infliximab (Remicade), for all but one of that biologic's approved indications, including for Crohn disease in adult and pediatric patients and ulcerative colitis in adult patients, rheumatoid arthritis in combination with methotrexate, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. The panel did not vote on the pediatric ulcerative colitis indication because it is protected by orphan drug exclusivity through September 23, 2018.

Remicade, an antitumor necrosis factor monoclonal antibody, was approved by the FDA in 1998. CT-P13 is approved in 67 countries (where it is known as Remsima) and is manufactured by South Korea–based Celltrion, Inc.

The FDA is likely to follow the panel's recommendation, as officials said Celltrion's data were convincing. Celltrion said it anticipates a decision by April.

Even the three committee members who voted against approval said they thought Celltrion had proven that CT-P13 was similar for most indications. But they were concerned about extrapolating results of Celltrion's trials, which were only conducted with patients with rheumatoid arthritis and patients with ankylosing spondylitis, to Remicade's inflammatory bowel disease indications. "I had great comfort with the package the sponsor put together," said Jeffrey Curtis, MD, William J. Koopman Endowed Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. But he said he was less certain about the drug's efficacy in Crohn disease and ulcerative colitis.

Janssen parent company Johnson & Johnson urged the panel to vote against approval for inflammatory bowel disease, saying that Remicade's mechanism of action is different for that condition. "Only direct clinical comparisons of CT-P13 and Remicade in active [inflammatory bowel disease] can provide the requisite assurance that CT-P13 is similarly safe and effective," said Jay Siegel, MD, chief biotechnology officer for Johnson & Johnson, at the meeting. He asked the FDA to wait for results from Celltrion's ongoing prospective, multicenter, observational cohort study in Hungary, which is looking at efficacy, safety, and immunogenicity of CT-P13 in induction and maintenance of remission in Crohn's and ulcerative colitis.

Both the FDA and Celltrion said the Hungarian study was merely confirmatory. "There is no reason to think there would be a surprising finding in the trial," said Alex Kudrin, MD, PhD, Celltrion vice president and head of clinical development.

Nikolay Nikolov, MD, clinical team leader at the FDA's Center for Drug Evaluation and Research, said the agency was not troubled and had not even requested the Hungarian trial. The study "is mostly to assure practicing clinicians that the drug is working," said Dr Nikolov.

Those who supported approval said it was with the hope that Celltrion and US partner Pfizer would bring a less costly drug to market. If CT-P13 is priced only marginally lower than Remicade, "I'm going to feel angry, embarrassed, and manipulated," said panelist Steven Solga, MD, chief of gastroenterology at St. Luke's University Hospital, Bethlehem, Pennsylvania.

Acting Committee Chair Liron Caplan said the FDA's approval pathway for biosimilars was created in part to widen access and reduce costs. If there's no price difference, "I would never prescribe it," said Dr Caplan, associate professor of medicine at the University of Colorado, Aurora.

Remicade has risen from $382 a vial to a current $1000 per dose, said Michael Epstein, MD, an Annapolis, Maryland, gastroenterologist who spoke at the public hearing. He said that CT-P13 offered the potential for a lower cost drug for his patients, who are facing increasingly higher deductibles. Celltrion reimbursed Dr Epstein's travel expenses.

Concerns About Substitution

Some of the committee members, along with physicians, patients, and advocates who spoke at the public hearing, said they were worried that the FDA's approval of CT-P13 could open the door to the drug being substituted for Remicade without a patient's or physician's knowledge.

Leah Christl, PhD, associate director of the therapeutic biologics and biosimilars staff at the FDA's Office of New Drugs, said that in general, "a prescriber can make an appropriate decision for their patient, either a treatment-naive patient or a patient that's already on existing therapy."

The law states that "an interchangeable product may be substituted for the reference product without the intervention of the healthcare provider who prescribed this product," but CT-P13 would not be considered interchangeable with Remicade, said Dr Christl.

However, the FDA does not have direct authority to regulate payer substitutions — that's the purview of state pharmacy boards, she said.

Clinicians had other concerns besides substitution. Angus Worthing, MD, who spoke on behalf of the American College of Rheumatology, requested distinct names and labels for biosimilars. "This will ensure correct prescribing," correct dispensing, and better long-term safety surveillance, said Dr Worthing, who practices in Washington, DC.

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