US FDA advisers narrowly back Sarepta's Duchenne gene therapy for accelerated approval

[May 13, 2023]  By Leroy Leo

(Reuters) -Advisers to the U.S. Food and Drug Administration on Friday narrowly recommended that the agency grant accelerated approval to Sarepta Therapeutics Inc's first-of-its-kind gene therapy for Duchenne muscular dystrophy (DMD).

Eight expert advisers voted in favor of the therapy, and six against.

Tabassum Ahsan, chair of the panel and vice president of cell therapy operations at California's City of Hope, said she was "very much on the edge" but ended up voting yes. She added that an ongoing confirmatory trial is going to be very influential going forward.

If approved, the potential one-time therapy could change the way patients with the muscle-wasting disease are treated, although the FDA earlier this week said the company did not provide "unambiguous evidence" that it will benefit patients with DMD.

Sarepta is hoping to gain approval through the FDA's accelerated pathway based on limited current data, and is conducting a late-stage trial to confirm the therapy's actual benefit to patients. Initial data from that trial is expected by December with more full results to be unveiled early next year.

The FDA is slated to make a decision on accelerated approval by May 29. The agency typically follows the advice of its expert advisers but is not obligated to do so.

"We still are in an area where there is a lot of uncertainty," said top FDA official, Peter Marks. "A small majority felt there was enough evidence here that was compelling to them and with a confirmatory trial ongoing, provided that was completed, they felt comfortable moving forward."

DMD is estimated to affect one-in-3,500 male births worldwide, according to the National Organization for Rare Disorders, causing progressive muscle failure. Most people with DMD do not survive beyond their thirties.

Signage is seen outside of the Food and Drug Administration (FDA) headquarters in White Oak, Maryland, U.S., August 29, 2020. REUTERS/Andrew Kelly/File Photo

During the public hearing portion of the meeting, Melanie Hennick made a plea for approval, saying that after receiving the therapy in a trial, her son Connor, 12, "is living with Duchenne, not suffering from it." "We know this treatment is not a cure, but it is an extremely significant difference," she said.

Sarepta's currently approved DMD therapies only treat a subset of patients with certain gene mutations. Other treatments include corticosteroids that have side effects if used long-term, such as excess weight gain and osteoporosis.

Pfizer Inc is also testing a DMD gene therapy.

Marks told the panel that the agency had decided to hold the advisory meeting, after initially not planning one, with the idea that an open public discussion would be important for Sarepta's approval application.

In a mid-stage trial, Sarepta's gene therapy was able to produce a mini version of the dystrophin protein needed to help keep muscles intact, but did not improve patient clinical outcomes like walking and standing ability.

During the meeting, advisers voiced concerns about moving forward without more evidence, given mixed results from the midstage trial.

Marks said in March the FDA is moving to encourage use of disease related biomarkers that may predict efficacy for gene therapies for diseases with small patient populations rather than waiting for definitive proof of patient benefit.

(Reporting by Leroy Leo and Aditya Samal in Bengaluru; Editing by Deena Beasley and Bill Berkrot)

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