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In the latest twist surrounding Sarepta Therapeutics and its rare disease drug, the US Food and Drug Administration has asked the company to provide additional data to review, a move some see as a sign that the agency is looking for ways to approve the treatment. Shares in Sarepta, which disclosed the data request Monday night, jumped more than 25 percent Tuesday.

The request comes amid ongoing uncertainty over the fate of a medicine being developed to combat Duchenne muscular dystrophy, which destroys muscle fibers and eventually confines boys to wheelchairs before sending them to an early death. There are no treatments currently available, and the FDA recently rejected two other medicines, sparking a heated clash over the fate of the Sarepta drug.

As pressure mounts from parents and lawmakers, the agency has been sending mixed signals about its intentions. In recent months, agency medical reviewers repeatedly questioned the veracity of a 12-person clinical study and underlying trial data. But at the same time, a high-ranking FDA official recently — and very publicly — noted the dangers in failing to approve drugs for “devastating diseases.” And last month, the agency delayed making a decision.


The controversy increasingly resembles the fracas over HIV drugs three decades ago. And the FDA appears caught between its mandate to adhere to scientific standards for approving medicines and finding ways to appease the public and authorize treatments for unmet medical needs. The Sarepta drug, however, poses a challenge, thanks to uncertainty about the trial data.

“I would just say there’s a process that has to take its course, and if there’s any interference in a process like that, it creates problems for everybody else,” Dr. Robert Califf, the FDA commissioner, told STAT. “… I think the smart thing to do is look at the extrapolation to other situations. … We want patients involved, all that sort of thing. This is just a very unusual situation.”


But after an FDA advisory panel voted in April that the Sarepta drug, known as eteplirsen, did not appear effective, the likelihood the agency would approve the drug appeared dim. At the same time, the panel had a decidedly mixed view about whether the drug generated enough dystrophin to produce a clinical benefit. Without this protein, muscle fibers degenerate and voluntary movement becomes impossible.

This explains why the FDA request is now triggering hopes the drug may be approved, after all.

The agency asked Sarepta for muscle biopsies from 13 boys who are participating in an ongoing trial in order to determine the extent to which the medicine may produce dystrophin. Sarepta said the data will be given to the agency “in coming weeks.” The request was unexpected and suggests that FDA officials are trying to find a way to endorse the drug.

“We believe it signals a clear indication that the agency is willing to grant eteplirsen accelerated approval,” wrote RW Baird analyst Brian Skorney in an investor note. Accelerated approval, by the way, refers to relying on a substitute outcome in a clinical trial to suggest a drug may have, but does not guarantee, a benefit. In this case, dystrophin production may be considered to be such a substitute.

Such views are a notable turnabout from the gloom hanging over Sarepta last week, when the FDA released final guidelines for allowing drug makers to provide experimental treatments to terminally ill patients. Some investors thought the FDA took the opportunity to release the rules as a way to sidestep approving the Sarepta drug, although Califf has denied this was the intent.

Nonetheless, some speculate the data request may also be a way for the agency to ensure it can later defend a decision not to approve the drug.

“We believe these FDA actions prolonging the eteplirsen review further could simply be designed to acknowledge the demands from all stakeholders — without changing their ultimate stance on the need (for Sarepta) to employ a proper drug development program,” wrote Leerink analyst Joseph Schwartz. Such a program would involve a traditional study that would take an undetermined amount of time.

Similarly, RBC Capital Markets analyst Simos Simeonidis maintained that the FDA “appears to leave no stone unturned in its attempt to explore every possible pathway and scenario under which it could possibly approve a drug that under almost every other circumstance we can think of would have been rejected, given the severe weaknesses and deficiencies in (the Sarepta) dataset.”

Yet Simeonidis continues to believe that the odds are against approval. “Our view remains that the agency will not set the precedent of approving a drug with such a limited dataset. On the other hand, we cannot overlook the tremendous pressure being put on the FDA, and it is very difficult to gauge what may happen behind the scenes at the agency at the last minute.”

Meghana Keshavan contributed reporting.

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