After taking several additional months to make its decision, the FDA has overruled its advisory committee and approved eteplirsen (Exondys 51) to treat Duchenne muscular dystrophy (DMD), the agency announced.
The drug will be specifically indicated for patients who have a confirmed mutation of the dystrophin gene, which will make them more likely to respond to exon 51 skipping, the mechanism by which the drug works, the agency said. About 13% of the DMD population has this mutation.
The approval follows a grim picture painted by an agency advisory committee last April, which decided the data provided by drugmaker Sarepta Therapeutics didn't provide substantial evidence that the drug actually increased dystrophin levels.
But in a letter that accompanied the FDA approval press release, CDER director Janet Woodcock, MD, said the company has since provided additional data that provide "substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level."
"The approval of Exondys 51 reflects FDA's ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework," Woodcock said in that letter. "In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children."
"These factors, combined with the dystrophin production data – and the drug's low risk profile – led the Agency to approve the drug under the accelerated approval pathway," she said.
The FDA faced intense public pressure to approve eteplirsen, as heard in desperate pleas from patients, parents, and advocates during an unusually long public comment period at the April advisory committee meeting. The patient representative on the panel broke down in tears over concerns that the data were inadequate to support the magnitude of benefit reported by many patients, and one wheelchair-bound patient cursed loudly and ran his chair into several empty chairs before rolling out of the room.
Tensions were especially high, as another exon-skipping drug, drisapersen (Kyndrisa) was rejected by the agency last January. Drugmaker BioMarin subsequently shuttered the program in May.
Eteplirsen was supposed to be reviewed in November 2015, at the same time as drisapersen, but that hearing was delayed. Following the rescheduled April hearing, the agency extended the PDUFA date of eteplirsen indefinitely.
The drug was approved under the FDA's accelerated approval program, which allows for an approval decision to be made based solely on efficacy data from a surrogate endpoint -- in this case, dystrophin production -- that is "reasonably likely to predict a clinical benefit to patients," the agency said.
FDA will require Sarepta to conduct a clinical trial to test whether the drug can actually meet a clinical endpoint of preserving motor function.