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FDA reversal sets up high-stakes hearing on Sarepta gene therapy

Dive Brief:

  • The Food and Drug Administration will convene a panel of experts to review Sarepta Therapeutics’ application for approval of a muscular dystrophy gene therapy in a regulatory U-turn that injects new uncertainty into the agency’s high-stakes review.


  • The decision is a reversal from just several weeks ago, when the FDA confirmed to Sarepta it would not hold an advisory committee meeting for the treatment, which is known as SRP-9001 and designed to treat the progressive muscle-wasting disease Duchenne.


  • Shares in Sarepta fell by 20% at market’s open Friday, reflecting investor concerns that the FDA’s change in position might signal debate at the agency over whether to approve Sarepta’s treatment. Wall Street analysts who cover the company still expect an OK, however.

Dive Insight:

Sarepta’s treatment could become the first gene therapy for Duchenne, a devastating genetic disorder for which the biotechnology company has successfully developed three other drugs. The benefit of those medicines is seen as limited at best, however, and they are only cleared for use in limited groups of Duchenne patients. SRP-9001 promises to more significantly alter the disease’s course, replacing the defective gene that’s behind it with a functional version.

Clinical trial results have shown the treatment can boost levels of the crucial dystrophin protein that gene encodes, albeit in a different, truncated form. And the data were more mixed on whether that effect readily translates to improved muscle and motor function. Sarepta is seeking an accelerated approval, which is based on whether a “surrogate” biomarker — like protein levels — can be “reasonably likely” to predict a clinical benefit.

The FDA’s initial decision not to hold an advisory committee meeting was therefore viewed by analysts as a positive sign the agency was reasonably convinced by the relationship between higher protein levels and clinical benefit. The change in position, to some, suggests ongoing debate.

“It may signal the FDA is still seeking to get more comfortable with microdystrophin as a surrogate, and does add some risk to approvability and timelines,” wrote Brian Abrahams, an analyst at RBC Capital Markets, referring in a client note to the shortened form of the dystrophin gene Sarepta’s treatment uses. (Sarepta’s other drugs were approved on an accelerated basis for their ability to raise levels of dystrophin protein.)

Brian Skorney, an analyst at Baird, had a similar view. The “inconsistency in communications from the FDA may be a signal of more internal debate than previously anticipated,” he wrote in a note to clients. But, “at the end of the day, we think SRP-9001 more than meets the statutory threshold of: ‘reasonably likely to predict benefit,’” he added.

In a statement late Thursday afternoon, Sarepta attributed the shift to the FDA’s interest in more thoroughly exploring how surrogate biomarkers could be used to support evaluation of cell and gene therapies. The agency has also recently reshuffled the office responsible for reviewing the complex treatments, which, on a conference call Thursday, Sarepta executives indicated played a role as well.

“I am, of course, disappointed to announce a change in the division’s decision about an advisory committee so soon after we informed you that [the FDA office responsible] did not intend to hold an advisory committee,” said Sarepta CEO Doug Ingram on the call. “But my disappointment is limited to the timing of these decisions, not with the substantive decision to hold an advisory committee.”

Sarepta indicated it’s prepared to present its case for approval at the meeting, which the FDA has told the company will be held before the currently scheduled May 29 decision date for SRP-9001.

The meeting will be a closely watched event, likely drawing significant input from members of the Duchenne patient community. In 2016, an advisory committee meeting for Sarepta’s first Duchenne drug, now approved as Exondys 51, was a contentious and dramatic affair.