Sarepta tests FDA flexibility with bid to expand Duchenne gene therapy’s approval

Sarepta Therapeutics has asked the Food and Drug Administration to expand approval of its gene therapy for Duchenne muscular dystrophy, banking on the regulator’s flexibility in reviewing conflicting clinical trial data.

The biotechnology company is requesting the FDA clear its treatment, called Elevidys, for people with Duchenne and a confirmed mutation in the relevant gene. Currently, Elevidys is approved only for patients aged 4 through 5 years old who can still walk. The neuromuscular disease, which primarily affects boys, progressively wastes away the muscles of affected individuals, often confining them to a wheelchair at an early age.

Elevidys is meant to compensate for the genetic mutations that cause Duchenne. Delivered via an engineered virus, it delivers instructions for a shortened form of a crucial-muscle protecting protein that treated patients lack.

Sarepta won a conditional clearance from the FDA in June on the basis of evidence showing Elevidys led to production of that protein, micro-dystrophin, which the agency judged was “reasonably likely” to translate to clinical benefits. The biotech had a late-stage study ongoing designed to prove whether it did.

However, in late October, Sarepta said that study actually missed its main goal. Treatment did not show a statistically significant difference from placebo on a functional scale known as the North Star Ambulatory Assessment. Trial participants treated with Elevidys improved by 2.6 points, compared to 1.9 points among those given the placebo.

Sarepta pointed to what it described as consistent treatment benefit on a number of other measures, such as how quickly participants could rise or walk 10 meters. While typically a negative primary result would necessitate further study, Sarepta said the disease’s severity and the collective picture painted by Elevidys’ data made it appropriate to expand the treatment’s approval.

Friday’s application puts the ball in the FDA’s court. The agency has pledged flexibility in considering drugs for disease like Duchenne, and already shown it in the course of reviewing Elevidys the first time. High-ranking FDA officials have also been closely involved in discussions, and the regulator faces pressure from patient groups to move quickly.

The biotech is asking for a priority review, which would begin a six month evaluation rather than the standard 10 if the FDA accepts Sarepta’s application.

The company is also asking the FDA to convert Elevidys’ conditional approval into a full one, which would secure the treatment’s place on the market. As the failed trial was meant to be confirmatory, the FDA technically could move to withdraw Elevidys, but analysts who cover the company view that prospect as unlikely.

In notes to clients Friday, however, some expressed uncertainty over whether the FDA would sign off on as wide an expansion as Sarepta has requested.

“Given the totality of the data, our understanding of the agency’s interactions with [Sarepta] up until this point, and the unmet need in [Duchenne], we continue to believe that Elevidys will remain on the market with an expanded label, at least for those ambulatory (without an age restriction), while expansion into non-ambulatory patients remains more of a wildcard,” wrote Joseph Schwartz, of Leerink Partners.

RBC Capital Markets’ Brian Abrahams, meanwhile, indicated he expected a “somewhat intensive process,” possibly to include the FDA convening a meeting of independent advisers.

Outside of the U.S., Sarepta’s partner Roche is responsible for regulatory discussions and commercialization.

Sarepta shares rose by about 3% in Friday morning trading. 

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