The response letter indicated the need for additional clinical data in order to further evaluate sirukumab's safety profile.
The US Food and Drug Administration (FDA) elected to issue a complete response to Janssen Pharmaceuticals for sirukumab (Plivensia), a treatment for moderately to severely active rheumatoid arthritis (RA) in adults who have had an intolerance to 1 or more disease modifying anti-rheumatic drugs (DMARDs) or inadequate response to prior treatment.
The FDA stated that there was a need for additional clinical data in order to further evaluate sirukumab's safety profile. Delivered as an injection, the anti-interleukin (IL)-6 monoclonal antibody’s mechanism of action is to block the IL-6 pathway in a way that is unique compared to currently approved RA therapies.
"We are disappointed by this development as we feel the data accumulated to date support the efficacy and safety of sirukumab in the treatment of moderately to severely active rheumatoid arthritis," Newman Yeilding (pictured), MD, the head of immunology development at Janssen’s development and research group, said in a statement. "We believe sirukumab represents an important therapeutic option for patients living with rheumatoid arthritis, especially for those individuals who cycle through multiple treatments and continue to struggle to find an effective option for a potentially disabling disease. We are reviewing the details of the complete response letter and plan to have a follow-up discussion with the agency to gain a full understanding of FDA requirements for US approval."
The drug was previously advised against by the Arthritis Advisory Committee of the FDA, citing safety concerns, on August 2, 2017.
“We appreciate the advisory committee’s thoughtful review and discussion of the sirukumab efficacy and safety data during today’s meeting. While the committee voted unanimously in support of the efficacy data, there was uncertainty regarding the safety profile,” Yeilding said at the time.
Sirukumab was reviewed based on data from a phase 3 global clinical development program involving 5 studies and more than 3000 patients. The drug was studied at 50 mg and 100 mg doses, administered every 4 and 2 weeks, respectively.
“Each time we get a new tool to use with patients, there are always many people who can benefit from that drug,” Angus Worthing, MD, the chair of the American College of Rheumatology’s Government Affairs Committee, told MD Magazine. “I think rheumatologists are aware of all of the safety concerns of the drugs we use, and if the drug is approved by the FDA, rheumatologists are able to bring up those concerns with their patients, and discuss the possibility of risks, and weigh those risks against the potential benefits of the drug.”
The most common adverse events included colds, upper respiratory tract infections, and redness, pain, or swelling at the injection site, as well as laboratory abnormalities. Serious infections, such as pneumonia, gastrointestinal perforations, and cellulitis, among others, were also observed in the studies.
Most concerning, the clinical trials experienced the presence of cardiovascular adverse events, including malignancies and mortality.