- Johnson & Johnson's chances of securing U.S. approval for its experimental arthritis drug sirukumab took a hit Wednesday, when an advisory panel to the Food and Drug Administration voted against recommending approval for the IL-6 blocker due to safety concerns.
- Committee members judged that sirukumab's benefits did not outweigh the safety risks seen in clinical study of the drug by a vote of 12-1, taking specific note of increased overall mortality amongst sirukumab-treated patients versus those receiving placebo.
- J&J, unsurprisingly, took issue with the committee's assessment. "We are disappointed and disagree with the group’s interpretation of the sirukumab benefit-to-risk profile," said Newman Yeilding, head of immunology development at J&J's subsidiary Janssen, in a statement.
J&J has previously flagged sirukumab as a potential blockbuster. A rejection by the FDA, if it occurs, would be a blow to the pharma giant's plans to strengthen its immunology portfolio.
The anti-TNF inhibitor Remicade (infliximab), which J&J sells in the U.S., remains the company's top-selling pharmaceutical. Yet the launch of two biosimilar versions to Remicade in the U.S. threatens to eat into J&J's market share and put pressure on pricing.
Sirukumab would give J&J a new offering in arthritis to pair with its recently approved psoriasis drug Tremfya (guselkumab). Those plans are now in doubt, as Wednesday's vote raises the likelihood the FDA rejects sirukumab.
Advisory panel votes are non-binding and the FDA is not required to follow the committee's recommendations, although it usually does.
The FDA recently turned down baricitinib, another arthritis contender developed Eli Lilly, due to concerns with increased thromboembolic events seen in studies of the drug. In that case, the regulator requested another clinical trial, which would significantly delay a resubmission. While the two drugs have different mechanisms of action and clinical profiles, barictinib's rejection signals the FDA is taking a hard look at safety for new arthritis hopefuls.
J&J also recently lost its development partner for sirukumab, with GlaxoSmithKline dropping its rights to the drug amid a broader shake-up of its R&D pipeline.
Conflicting views on safety
In a briefing document prepared for Wednesday's advisory committee meeting, J&J argued the cardiovascular events observed in sirukumab's trials were in line with the known co-morbidities amongst rheumatoid arthritis (RA) patients.
"Major adverse cardiovascular events (MACE) and malignancies were observed in clinical studies of sirukumab, and rates of these events were consistent with expected rates in patients with RA," Janssen wrote in its presentation of sirukumab's safety profile.
FDA staff, however, took a different view — one that appeared to carry more weight with the experts on the Arthritis Advisory Committee.
"While these immunosuppression-related adverse events and laboratory parameter changes were in qualitative terms similar to other products targeting the IL-6 pathway, the observation of the trend of increased overall mortality seen within the controlled time period of registration studies seems unique for the sirukumab program," FDA staff wrote in the regulator's briefing document for the panel.
A total of thirteen patients died from MACE through 16 weeks following administration of sirukumab in the Phase 3 studies of the drug, with another 11 deaths due to infections of malignancy. Janssen noted that each fatal cardiovascular event involved patients who had at least two risk factors on top of their rheumatoid arthritis.
Looking more at cardiovascular events more broadly, seven patients had non-fatal heart attacks and 14 experienced non-fatal strokes.