The clock is ticking down to the FDA advisory committee meeting about Sarepta Therapeutics’ Duchenne muscular dystrophy (DMD) gene therapy SRP-9001. With days to go, Sarepta has set out what is expected to be asked at the meeting—and made the case that it can allay concerns about its confirmatory trial.
Talking to investors on the first-quarter results conference call, Sarepta CEO Doug Ingram said he expects the question of “whether the totality of evidence supports the conclusion that SRP-9001 dystrophin protein at the levels expressed by this therapy is reasonably likely to predict clinical benefits” to be a big part of the discussion at the advisory committee meeting.
“The totality of the evidence will include natural history, the preclinical data, biomarker results and the functional results from our clinical trials. The panel will also address the risk-benefit analysis associated with the administration of SRP-9001 for the treatment of ambulatory patients with DMD in the context of accelerated approval,” the Sarepta CEO said.
Ingram added that the panel will assess the ability of Sarepta to complete a confirmatory trial for the gene therapy. The biotech has a poor track record in that regard. Sarepta won accelerated approval for its first DMD drug, Exondys 51, in 2016 on the basis of a small, single-arm clinical trial. Almost four years later, the biotech began the confirmatory trial—which has yet to finish.
The FDA criticized the delay in the complete response letter for another Sarepta drug, stating (PDF) that the biotech’s “failure to initiate eteplirsen’s confirmatory study with due diligence is very concerning to FDA and is of concern to the public.” The FDA pulled a U-turn and approved that drug, Vyondys 53, later in 2019. Confirmatory trials of Vyondys 53 and another Sarepta drug, Amondys 45, are ongoing.
With Sarepta yet to provide confirmatory clinical trial results on three drugs almost seven years after the first accelerated approval, the FDA and advisory committee may have questions about how long it will take the biotech to provide more data on SRP-9001. Ingram thinks the status of Sarepta’s confirmatory trial, EMBARK, puts it in a strong position to allay any concerns.
“One of the obviously reasonable questions one would pose is, ‘are you confident that if we give you an approval now on an accelerated basis, that EMBARK will in fact complete?’ EMBARK actually was fully enrolled as of September of last year, so I think relative to other accelerated approval therapies we are in a particularly advantageous, brilliant position with respect to the completion of our confirmatory trial,” Ingram told investors. “There's no risk, zero risk [that accelerated approval could affect the study].”
Mizuho Securities analysts picked up on the discussion, writing in a note to investors that “interestingly, the AdComm panel expects to assess the company's ability to conclude the confirmatory EMBARK trial in a timely manner.” Sarepta expects data from EMBARK around the end of the year.
While Ingram engaged with analysts about EMBARK, he otherwise declined to answer questions about the advisory committee. One analyst asked whether Sarepta has seen the FDA’s briefing documents, which will indicate how the agency views the application, but was rebuffed by Ingram.
“We're going to stay very focused on prosecuting our BLA, preparing for our AdComm, we're not going to discuss the AdComm or the briefing books or the regulatory process right now. I'm not going to answer your questions on the regulatory process through the advisory committee until after May 12,” the CEO said.
The advisory committee meeting is scheduled for May 12.