Faced with a big red flag regulators raised on safety, a panel of outside experts turned thumbs down on approving J&J’s sirukumab for rheumatoid arthritis, concluding that there wasn’t a clear enough understanding of the drug’s safety profile to justify the risk of putting it on the market.
The vote was 12 to 1 against the drug, saying that the safety profile did not justify an OK. That was the key issue, and they followed up by the same numbers in a formal vote against an approval.
Harvard Med’s Dan Solomon summarized the thoughts of the majority, saying he voted no “based on not feeling confidence about the safety of this drug.”
Several of the experts shook their heads over what they agreed were troubling but mysterious evidence that there was an imbalance in deaths among the trial patients taking the drug. While J&J insisted that the overall evidence indicated that the risk/benefit ration justified an approval, some of the experts also wondered why they would approve another IL drug with troubling safety signals while two other such drugs were already on the market that didn’t have the same safety problems.
The group, though, were satisfied that researchers had provided ample efficacy data to demonstrate the drug’s value.
The FDA is not obligated to follow the panel’s lead, but generally does. Even if it should be approved against all odds, the experts on the panel made it clear that a formulary committee would have no trouble either refusing reimbursement or restricting it as an absolute last resort, severely limiting any market potential.
J&J, though, has little choice now but to play this one out.
“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,” said Newman Yeilding, head of immunology development, Janssen Research & Development, in a statement. “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.”
J&J was facing an uphill fight on this quest. The FDA has already reinforced just how sensitive it is on safety issues when it rejected Eli Lilly’s baricitinib and demanded another study to prove its safety. Then GlaxoSmithKline dumped its rights in the drug just days ago, leaving J&J to go on alone.
In an internal review at the FDA, regulators concluded:
Wide confidence intervals around treatment comparisons for serious rare events such as death, malignancy, and MACE indicate that the imbalances could be due to chance but also that relatively large increases in risks on sirukumab cannot be ruled out based on the data alone. Such imbalances raise concern regarding these important safety risks. Additional safety signals related to events of GI perforation and hypersensitivity were also observed.
J&J may well face whether it wants to buckle down and do a major safety study ahead of a formal decision, or give it up and move on. It won’t be an easy decision.
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