The US Food and Drug Administration's (FDA's) Arthritis Advisory Committee voted unanimously to recommend licensure of ABP 501 (Amgen Inc) as a biosimilar product to US-licensed Humira (adalimumab) (AbbVie, Inc) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease, adult ulcerative colitis, and plaque psoriasis.
The FDA approved adalimumab on December 31, 2002. It is currently licensed for treatment of these and other conditions.
"I thought the information we were given about biosimilarity in terms of the analytics was excellent," said temporary voting member David J. Margolis, MD, PhD, professor of dermatology and epidemiology, University of Pennsylvania School of Medicine, Philadelphia.
The 26-member voting committee comprised healthcare professionals with a wide range of clinical and professional expertise.
Adalimumab is a human monoclonal antibody that inhibits tumor necrosis factor alpha and is administered subcutaneously. ABP 501 is available in a single-use prefilled syringe and a single-use autoinjector at strengths approved for adalimumab in the United States (ie, 20 mg/0.4 mL and 40 mg/0.8mL for the prefilled syringe, and 40 mg/0.8 mL for the autoinjector). The dosage form and route of administration are the same as those approved for US-licensed adalimumab.
The Biologics Price Competition and Innovation Act of 2009 provides an abbreviated approval pathway for biological products shown to be biosimilar to or interchangeable with a biological product (the "reference product") that is already licensed by the FDA. This licensure pathway falls under section 351(k) of the Public Health Service Act and allows the FDA to rely on certain existing scientific knowledge about the reference product's safety and effectiveness to license a biosimilar biological product on the basis of fewer preclinical and clinical data about that specific product than is otherwise required.
Clinical Studies in Patients With Rheumatoid Arthritis, Plaque Psoriasis
The committee's decision follows a discussion of data from a single-dose pharmacokinetic (PK) study and two clinical trials.
The PK study (study 217) was a three-way comparison of ABP 501, US-licensed adalimumab, and European Union (EU)–approved adalimumab that supported the PK similarity of ABP 501 and US-licensed adalimumab.
Study 262 was a 26-week, randomized, double-blind, parallel group study that included 526 patients with moderately to severely active rheumatoid arthritis who were receiving background methotrexate. The study randomly assigned patients in a 1:1 ratio to receive ABP 501 or US-licensed adalimumab at a dose of 40 mg subcutaneously every other week. The study's primary endpoint was the proportion of patients who stayed in the study and achieved an American College of Rheumatology 20% response at week 24. The study showed there were no clinically meaningful differences in the safety, purity, or potency of the two drugs.
Study 263 was a randomized, double-blind, parallel-group study that was conducted outside the United States. It included 350 patients with moderate to severe plaque psoriasis who were randomly assigned in a 1:1 ratio to receive 80 mg of EU-approved adalimumab or ABP 501 subcutaneously on day 1, then 40 mg every 2 weeks beginning 1 week later. At week 16, patients in the EU-approved adalimumab group were randomly assigned to undergo a single transition to ABP 501 or continue to receive EU-approved adalimumab through week 48. The study's primary endpoint was the percent improvement in Psoriasis Area Severity Index score from week 1 to week 16. The transition from EU-approved adalimumab to ABP 501 showed no difference in the safety or immunogenicity profile of ABP 501. "This would support the safety of a clinical scenario where non-treatment naive patients may undergo a single transition to ABP 501," the FDA writes in its brief.
The company also provided extensive data addressing the scientific justification for extrapolation of data supporting biosimilarity in the treatment of juvenile idiopathic arthritis in patients aged 4 years or older, psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease, and ulcerative colitis.
During the open public comment session, 20 patients and patient advocates weighed in on several issues. They had mixed views on extrapolating clinical data from patients with rheumatoid arthritis and plaque psoriasis to those with other conditions, including adult Crohn's disease and ulcerative colitis. Some said the ability to extrapolate data between differing patient populations is critical to the development of biosimilar products, but others felt that doing so is inappropriate and risky.
Many of the public speakers voiced concern about the possibility that patients who are stable while receiving treatment with one biologic will be switched to a biosimilar for nonmedical reasons, which could potentially jeopardize their health.
These concerns are not new, several committee members said. A number of committee members expressed dismay that these issues are still largely unresolved and urged the FDA to address patients' concerns.
"I've not seen such a disconnect between the charge to the committee and these concerns of the public.... The disconnect is really quite remarkable.... These are essential issues, and they need some forum to be aired out fully and completely," said temporary voting member Steven F. Solga, MD, a gastroenterologist in private practice in Bethlehem, Pennsylvania.
"I felt like the totality of evidence supported licensure and also extrapolation to the other indications. I want to support the public's concern about nonmedical switching," said temporary voting member Alyce M. Oliver, PhD, MD, professor of medicine, director, Rheumatology Fellowship Training Program, and ambulatory medical director of medicine, Medical College of Georgia, in Augusta.
Postmarketing Studies Needed
Several committee members remarked on the need for postmarketing studies and improved monitoring. "My main concern was the lack of clinical data, both for inflammatory bowel disease as well as for the pediatric indication. The evidence still was strong enough for me to vote yes. Given that there's [a] lack of clinical evidence, it's important to have a specific, deliberate, prospective, postmarketing surveillance study, and I would suggest something that's not voluntary [but is] more deliberate than that," said temporary voting member Jeremy Adler, MD, director, Pediatric Inflammatory Bowel Disease Program and assistant professor of pediatric gastroenterology and health services research, Child Health Evaluation and Research Unit, C. S. Mott Children's Hospital, University of Michigan, in Ann Arbor.
"I find it shocking that in 2016, we're still only relying on passive systems like Sentinel and Medwatch and that we don't have mandatory postmarketing studies, not just for biologics but also for drugs and devices that are approved on these sorts of pathways," Dr Margolis said.
FDA AAC brief. Published online July 12, 2016. Full text, Errata
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Cite this: Biosimilar to Humira Recommended by FDA Panel - Medscape - Jul 13, 2016.