FDA
13th October 2017

FDA’s Arthritis Advisory Committee Does Not Recommend Sirukumab For Treatment Of Moderately To Severely Active Rheumatoid Arthritis

On August 2nd, the U.S. Food and Drug Administration’s Arthritis Advisory Committee (AAC) discussed biologics license application (BLA) 761057, for sirukumab (proposed trade name PLIVENSIA™) for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs (DMARDs).

FDA’s Arthritis Advisory Committee Does Not Recommend Sirukumab For Treatment Of Moderately To Severely Active Rheumatoid Arthritis

On August 2nd, the U.S. Food and Drug Administration’s Arthritis Advisory Committee (AAC) discussed biologics license application (BLA) 761057, for sirukumab (proposed trade name PLIVENSIA™) for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs (DMARDs).

Sirukumab, developed by Janssen Biotech, Inc. is an anti-interleukin (IL)-6 monoclonal antibody that binds specifically with high affinity to the cytokine IL-6, preventing IL-6-mediated signaling. Sirukumab blocks the IL-6 pathway differently than the other IL -6 receptor inhibitors currently approved for the treatment of RA, tocilizumab (ACTEMRA®) and sarilumab (KEVZARA®).

The AAC reviewed safety and efficacy data from Janssen’s clinical development program which included two pivotal Phase 3 studies designed to evaluate sirukumab 50 mg every 4 weeks and 100 mg every 2 weeks, given subcutaneously in combination with background DMARDs; and a 1-year active comparator study in biologic-naïve patients with active RA who were intolerant to methotrexate. The proposed dose was 50 mg subcutaneously every 4 weeks for the desired indication.

At this meeting, there were 4 discussion questions and 3 voting questions pertaining to efficacy, the radiographic progression study, dose selection, safety, and recommendation for approval. Although the committee voted unanimously (13 to 0) in support of the efficacy data, there was uncertainty regarding the safety profile.  The data revealed a higher number of deaths in the sirukumab arms vs. placebo arms in the phase 3 studies. As such, the majority of the committee (Yes: 1, No: 12, and Abstain: 0) did not support for approval of sirukumab.

More information is available at 2017 Meeting Materials, Arthritis Advisory Committee

The agency is not obligated to follow its committee’s recommendation, but normally does so. On September 22nd, Janssen received a complete response letter from the FDA indicating the need for additional clinical data to further evaluate the safety of sirukumab. It was unclear to the committee whether the imbalance in mortality between sirukumab and placebo was a result of study design or whether it is a real safety signal. “I’m not sure whether the safety signal is of concern or not. I don’t think there’s enough data here to know that. It’s concerning, and it may be just noise, but it may also be real,” said temporary voting member, David T. Felson, MD, MPH. Janssen plans to have a follow-up discussion with the FDA to gain a full understanding of FDA requirements for U.S. approval of sirukumab.

Innovative Science Solutions (ISS) was happy to assist Janssen in the preparation for this complex and thoughtful advisory committee review. ISS has almost two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact info@innovativescience.net.

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