The Arthritis Advisory Committee of the U.S. Food and Drug Administration (FDA) recommends licensing Amgen’s ABP 501 as a biosimilar product to AbbVie’s FDA-approved Humira (adalimumab) for the treatment of patients with psoriatic arthritis, plaque psoriasis, rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis (patients age 4 and older), adult Crohn’s disease, and adult ulcerative colitis.
Humira has been an FDA-approved human monoclonal antibody for treating these and other conditions since Dec. 31, 2002.
“I thought the information we were given about biosimilarity in terms of the analytics was excellent,” temporary voting member David J. Margolis, MD, PhD, professor of dermatology and epidemiology at University of Pennsylvania School of Medicine, said in a press release.
Humira is a TNF-inhibiting anti-inflammatory biologic medication. It binds to tumor necrosis factor-alpha (TNFα), which normally binds to TNFα receptors, leading to the inflammatory response of autoimmune diseases. By binding to TNFα, Humira reduces this inflammatory response. It is administrated subcutaneously.
ABP 501 is available in a single-use prefilled syringe and a single-use autoinjector at strengths approved for Humira 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 Humira.
The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of President Obama’s Affordable Care Act. The BPCI Act created an abbreviated licensing pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product. This abbreviated licensure pathway permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and enables a biosimilar biological product to be licensed based on less than a full complement of product-specific data.
The committee’s decision follows a discussion of data from a single-dose pharmacokinetic (PK) study and two clinical trials:
A single-dose pharmacokinetic study (Study 217) provided a three-way comparison of ABP 501, U.S-licensed Humira, and EU-approved Humira and supported PK similarity of ABP 501 and Humira, and provided a pharmacokinetic bridge to support the relevance of the comparative data generated using EU-approved Humira to support a demonstration of the biosimilarity of ABP 501 to U.S.-licensed Humira.
A comparative clinical study (Study 262) between ABP 501 and EU-approved Humira in patients with rheumatoid arthritis (RA) supported a demonstration of no clinically meaningful differences in terms of safety, purity, and potency. This was a 26-week, randomized, double-blind, parallel group study conducted in 526 patients with moderate to severely active RA.
The study showed there were no clinically meaningful differences in the safety, purity, or potency of the two drugs.
A second comparative clinical study (Study 263) assessed the efficacy, safety, and immunogenicity between ABP 501 and EU-approved Humira in patients with psoriasis, and safety and immunogenicity in patients undergoing a single transition from EU-approved Humira to ABP 501.
This was a randomized, double-blind, parallel-group study conducted outside the U.S. in 350 patients with moderate to severe plaque psoriasis. The transition from EU-approved Humira 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 wrote.
Amgen also submitted comparative analytical data on the ABP 501 lots used in clinical studies intended to support a demonstration of biosimilarity in the treatment of juvenile idiopathic arthritis in patients ages 4 or older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis. Based the review, Amgen’s analytical data for ABP 501 demonstrated that ABP 501 is highly similar to U.S.-licensed Humira, notwithstanding minor differences in clinically inactive components
During the open public comment session, 20 patients and patient advocates noted some concerns, and they had mixed opinions on extrapolating data from patients with rheumatoid arthritis and plaque psoriasis to those with other diseases. Some said the ability to extrapolate results between differing disease is critical to the development of biosimilar products, but others felt that doing so is incorrect and unsafe.
Many of the public speakers voiced concerns about the chance 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 apprehensions are not new, some committee members said. Some members expressed apprehension that these matters are still unresolved and urged the FDA to address patients’ concerns.
Several committee members remarked on the need for post-marketing studies and improved monitoring to respond to the public’s concerns. “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, post-marketing surveillance study, and I would suggest something that’s not voluntary [but is] more deliberate than that,” said temporary voting member Jeremy Adler, MD.