A panel of arthritis experts has overwhelmingly recommended against the approval of Johnson & Johnson's sirukumab. The panel voted 12 to 1 against approving the IL-6 monoclonal antibody for the treatment of rheumatoid arthritis after taking a dim view of safety data presented by J&J.
J&J went into the meeting needing to convince the FDA arthritis advisory committee to downplay the significance of the imbalance in mortality seen in clinical development. Of the 35 deaths that occurred within 16 weeks of the last dose, 34 involved patients who received sirukumab. The FDA saw the main causes of death—cardiovascular disease and serious infections—as indicative of immunosuppressive effects. And J&J ultimately failed to shake this worry from the experts’ minds.
“[It was a] close call for me. I am sympathetic to the fact that I think there's a real possibility that the difference we're seeing in mortality is a bias. I just cannot completely shake the uncertainty about the mortality,” Erica Brittain, Ph.D., a mathematical statistician at the National Institutes of Health, said, according to a report in Medscape.
The mortality imbalance recurred repeatedly in the expert’s explanations of their “no” votes.
J&J was also taken to task for seeking too broad an indication. The prospect of clearing a drug linked to increased mortality for use in patients with moderate to severe rheumatoid arthritis who had tried one disease-modifying antirheumatic drug proved too much for most panelists, despite their belief in its efficacy. The 12 “no” votes on the safety and approval questions followed 13 “yes” votes on the efficacy question.
Some panelists may have overridden their concerns about mortality and voted “yes” if J&J’s drug was a breakthrough in terms of efficacy. But with Regeneron and Sanofi and Roche having already won approval for drugs that disrupt IL-6 signaling, albeit in a different way than sirukumab, most panelists saw little reason to take the risk of recommending J&J’s asset.
These competitive considerations will factor into J&J’s thinking if the FDA follows the panel’s recommendation and rejects sirukumab. That would likely leave J&J needing to run further studies to show sirukumab has a favorable risk-benefit profile. Whether J&J, which is flying solo after GlaxoSmithKline dropped sirukumab, sees such investment as worthwhile given rivals already have a head start will shape the future of the drug.