An FDA advisory committee agreed on Friday that Zevra Therapeutics had provided sufficient efficacy data supporting the approval of arimoclomol for Niemann-Pick disease type C.
The FDA’s Genetic Metabolic Diseases Advisory Committee on Friday voted in favor of Zevra Therapeutics‘ investigational drug arimoclomol for the treatment of Niemann-Pick disease type C.
In an 11-5 vote, the panel of external experts agreed that Zevra had provided sufficient evidence to support the efficacy of arimoclomol. Still, the advisory committee expressed reservations about the drug candidate, specifically the magnitude of its clinical benefit and the ambiguities related to its non-clinical data.
“I found the effect size to be small,” Jonathan Mink, a private consultant from New York and formerly a professor of neurology, neuroscience and pediatrics at the University of Rochester Medical Center, said during the meeting. Mink voted yes in favor of Zevra but conceded that it was a “very reluctant yes.”
“Overall, the bulk of the data favored a slightly positive effect,” Mink said. “I think the unmet need is very clear. I’m not sure that this meets that need, but on balance, I voted yes.”
Walter Kraft, professor of pharmacology, medicine and surgery at the Thomas Jefferson University in Pennsylvania, voted against Zevra, saying that arimoclomol “did not meet the evidentiary standards for approval.”
“I took the perspective of a regulatory standpoint that is created for rare diseases,” Kraft said. “I do worry about approval of drugs for which there is not unequivocal evidence of efficacy. That is not without harm also in terms of diversion of resources and activity within the space.”
Arimoclomol is a small molecule that can cross the blood-brain barrier and works by making cells hardier, allowing them to resist destruction even while under stress. The FDA previously rejected the drug candidate in June 2021. In its Complete Response Letter, the regulator laid out concerns with Zevra’s choice of metric for efficacy—the five-domain NPC Clinical Severity Scale (NPCCSS) that looked at swallowing, speech, fine motor, ambulatory and cognitive function in patients.
Zevra resubmitted arimoclomol’s application in December 2023 with a rescored NPCCSS, which removed the cognition domain and employed a modified swallow scale. In all, the biotech’s data package for arimoclomol consisted of just one well-controlled trial, the findings of which were supplemented by non-clinical studies performed on mice and cellular models.
In a briefing document published ahead of Friday’s adcomm meeting, the FDA again flagged “uncertainties” in Zevra’s application, especially in the biotech’s rescoring of the NPCCSS. The regulator also asked the panel of external advisors to discuss whether Zevra had provided enough evidence for arimoclomol and whether its data package was too thin to support approval.
