Sarepta Plunges After FDA Advisers Don't Back DMD Drug

  • Panel voted 7-3 that muscle drug wasn't shown to be effective
  • Shares fall 26 percent following Monday's FDA meeting

Sarepta Therapeutics Inc. plummeted Tuesday after it failed to win the backing of a panel of U.S. regulatory advisers for its experimental drug to treat a devastating muscle disease called Duchenne muscular dystrophy.

Advisers to the Food and Drug Administration voted 7-3, with three members abstaining, on Monday that there wasn’t enough evidence from a key clinical trial to show the drug is effective against the disease. Taken during an emotional and at times volatile public meeting, the vote was another setback for the company after it faced questions last week about testing of the drug, called eteplirsen. The shares fell 26 percent to $11.02 at the close Tuesday in New York.

Sarepta is trying to be first to market a treatment for the disease, which mainly affects young boys. The FDA will take the panel’s recommendation into consideration when it decides whether to approve eteplirsen, a decision scheduled to be made by May 26. The company’s stock was halted from trading during Monday’s all-day session.

The company said it will keep working with the FDA on the review.

“We remain committed to our mission of bringing a treatment to the Duchenne community,” interim Chief Executive Officer Edward Kaye said in a statement Monday.

Duchenne muscular dystrophy, or DMD, quickly worsens patients’ ability to walk and leads to breathing difficulties. Patients often die by age 25, usually from lung disorders, according to the National Institutes of Health.

High Emotions

Panel member Chiadi Onyike, an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, said he wished the studies could have accounted for dozens of patients who testified at the panel that the drug helped them. He encouraged patients to consider participating in placebo-controlled trials, where some would get the drug and others wouldn’t.

His comment about placebo trial set members of the audience screaming. One visibly upset patient in an electric wheelchair charged the panel, knocking through two rows of chairs. 

More than 50 patients and patient advocates spoke, many more than normal. The FDA has already rejected two previous drug candidates from BioMarin Pharmaceutical Inc. and PTC Therapeutics Inc.

“If you’re 100 percent sure this drug isn’t working then don’t approve it,” said a 13-year-old boy named Ryan, who said he has been on eteplirsen almost five years and can still walk, swim and play with his friends. “If you aren’t 100 percent sure, then approve it and help others like me.”

“Please don’t let me die early,” another boy pleaded.

Drug Data

Sarepta is seeking accelerated approval, which allows for clearance based on trial results that show an effect on patients that’s reasonably likely to predict benefit. In this case, the company measured whether the ability to walk in boys taking eteplirsen was degraded more slowly than those not treated, and whether the drug increases levels of the protein dystrophin, which is missing in Duchenne patients. If the FDA clears eteplirsen for sale, Sarepta would have to do more studies on the drug to prove its benefit and gain regular approval.

When FDA was first in discussions with Sarepta, “it was our understanding that dramatic increases in dystrophin were being observed,” Billy Dunn, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, told the panel earlier in the day. Instead, patients’ average dystrophin levels on the drug rose to 0.9 percent of normal levels, an increase that was “very disappointing,” said Eric Bastings, deputy director of the division of neurology products in FDA’s Center for Drug Evaluation and Research.

The FDA panel voted that the dystrophin levels produced by eteplirsen aren’t reasonably likely to predict clinical benefit.


A 17-year-old boy named Austin who, along with his brother Max, said he has been taking eteplirsen in Sarepta’s trials. He took issue with Bastings’s characterization of the dystrophin results.

“I can only guess that you don’t know anything about Duchenne,” he said. “Making 0.9 percent is amazing. It lets me feed myself. It keeps Max walking. It gives us a chance.”

If Sarepta’s drug is rejected, there are others aiming to gain approval. Marathon Pharmaceuticals LLC is studying a Duchenne treatment called deflazacort. The closely held company said it plans to file for FDA approval of the drug in May.

Sarepta’s key trial didn’t include a group receiving a placebo, normally the gold standard for clinical testing. Instead, the company compared patients getting the drug to data from external patient registries. That can create what’s known as expectation bias, FDA staff said, where the researchers conducting the trial interpret the results in a way that favors what they hoped would happen. The panel voted 7-5, with one abstention, that the design of the trial caused bias.

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