The FDA needs a wee bit more time to consider the approval of Sarepta Therapeutics' gene therapy for Duchenne muscular dystrophy (DMD), however, the agency has indicated an accelerated approval is likely in a restricted age group.
A week and a half after Sarepta’s SRP-9001 was the subject of an FDA advisory committee meeting, the company has provided an update on the regulatory process. Sarepta said that after discussions, the FDA has requested “modest additional time” to finish its review, which was previously expected to be done by May 29. Now, the decision will arrive by June 22. In the meantime, the FDA will work on finalizing label negotiations and postmarketing commitment discussions.
The delay should feel like deja vu for Sarepta. Back in 2016, the FDA requested more time to review the DMD med eteplirsen. The therapy was eventually approved as Exondys 51, although the decision—which arrived months after the original due date—proved controversial.
This time around, Sarepta has suggested that the decision on whether SRP-9001 will be approved for ambulatory patients with a DMD gene mutation has already been made. The company said the FDA has indicated that “it is working toward potentially granting an accelerated approval for SRP-9001, initially for use in Duchenne patients ages 4-5 years old.”
The restricted age range would reflect the FDA’s concerns that Sarepta did not have enough evidence to support use in older patients. In briefing documents prepared for the advisory meeting, the FDA said: “It is challenging to conclude with reasonable certainty from the data provided by the applicant either that SRP-9001 is likely effective for younger patients, or that it is likely ineffective for older patients or those with somewhat poorer functional status.”
Sarepta provided evidence from a post hoc analysis to show that results varied by age. Specifically, patients ages 4 to 5 showed improvement compared to placebo, while 6- to 7-year-old patients had worse function scores than placebo. The FDA said those data were “challenging to interpret.”
Nevertheless, the committee voted 8 to 6 that the benefit-risk profile of SRP-9001 was strong enough to support accelerated approval. One member argued that "we owe it to the patients to help them intervene."
The FDA has left the door open to a wider age range should the results of Sarepta’s phase 3 EMBARK trial meet its goals. That study will serve as the confirmatory trial for SRP-9001 to secure full approval. The accelerated pathway allows medicines to be approved based on a biomarker that reasonably predicts clinical benefit so long as the company completes such a trial.
Sarepta said EMBARK is already fully enrolled, and top-line results are expected in the fourth quarter.
With that update, Sarepta warned it “will remain in a quiet period” for the duration of the FDA’s review of the biologics license application for SRP-9001.
Despite news of a likely approval—albeit restricted to a smaller age group—Sarepta's shares dropped 15% to $125 in premarket trading Wednesday, compared to $146.91 at close.
Mizuho Securities analyst Uy Ear said "at best we believe the news is mixed." While it's great that the therapy will likely be approved, there will be a delay and the label will be narrow—at least until the EMBARK data comes out.
The FDA's hesitancy to approve for a wider age group makes that read out all the more crucial, according to Ear and William Blair Equity Research. But Ear said that investors seem to think that Sarepta could get away with a miss on statistical significance as long as SRP-9001 shows a trend towards clinical benefit.
William Blair agrees that there's leeway on what a positive readout looks like for Sarepta. The firm said that the potential age restriction means that the "focus on the confirmatory EMBARK data only intensifies."
Editor's note: This story was updated at 12:15 p.m. ET to include analyst commentary.