FDA Advisory Committee Votes Against Recommendation of Sirukumab

Sirukumab is designed to treat adults with moderately-to-severely active rheumatoid arthritis.

Yesterday, the FDA’s Arthritis Advisory Committee did not recommend the approval of sirukumab to treat adults with moderately-to-severely active rheumatoid arthritis (RA).

Sirukumab is an anti-interleukin (IL)-6 monoclonal antibody designed to block the IL-6 pathway in a different way than currently approved IL-6 inhibitors, according to a press release.

A Biologics License Application for sirukumab was submitted to the FDA on September 23, 2016, seeking approval to treat patients with RA who had an inadequate response or are intolerant to 1 or more disease modifying anti-rheumatic drugs (DMARDs).

“We appreciate the advisory committee’s thoughtful review and discussion of the sirukumab efficacy and safety data during today’s meeting,” Newman Yeilding, MD, head of Immunology Development at Janssen Research & Development, said in the release. “While the committee voted unanimously in support of the efficacy data, there was uncertainty regarding the safety profile. As a result, the committee did not support approval for the proposed indication. We are disappointed and disagree with the group’s interpretation of the sirukumab benefit-to-risk profile.

“We remain confident in the data accumulated to date supporting sirukumab in the treatment of moderately-to-severely active rheumatoid arthritis. We look to continue discussions with the FDA in their review of the application as we believe sirukumab represents an important therapeutic option for patients with rheumatoid arthritis.”

Although the FDA is not bound by the recommendation of the committee, their advice is taken into consideration.

The committee reviewed safety and efficacy data of sirukumab from a global phase 3 clinical development program inclusive of 5 studies and more than 3000 patients with RA, including those who continued to have active disease despite prior treatment with DMARDs and biologics, according to the release.

The patients were administered 50 mg of sirukumab every 4 weeks and a 100-mg dose every 2 weeks. Sirukumab demonstrated significant efficacy in treating RA by improving the signs and symptoms of the disease and inhibiting the progression of structural damage, according to the release. Improvement was also observed in patient-reported outcomes measures including fatigue, pain, physical function, and quality of life.

The most commonly reported adverse events (AEs) were laboratory abnormalities, colds, upper respiratory tract infections, and redness, pain, or swelling at the injection site.

Serious AEs were serious infections such as pneumonia and cellulitis, abscess, sepsis, osteomyelitis, hypersensitivity reactions, low platelets, lipid elevations, and gastrointestinal perforations.

Cardiovascular AEs, malignancies, and mortality were reported in the clinical studies of sirukumab, according to the release.

“Rheumatoid arthritis continues to be a disease with a high unmet need for many patients who are intolerant to or lose response over time to currently available treatment options,” Sergio Schwartzman, MD, Weill Cornell Medical College, Hospital for Special Surgery, New York Presbyterian Hospital, said in the release. “The availability of alternative treatment options, including a new molecular entity like sirukumab, is critically important in my ability as a practicing rheumatologist to help patients control their disease, especially considering the complexity and heterogeneity of an autoimmune disease like rheumatoid arthritis. It is my hope that the FDA carefully considers all of the phase 3 data and the current need for additional rheumatoid arthritis treatment options on behalf of patients and practicing rheumatologists.”