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In rather blunt language, a team of Food and Drug Administration reviewers believe that a drug developed by Sarepta Therapeutics is unlikely to benefit children suffering from Duchenne muscular dystrophy. The rare disease causes muscles in boys to stop working and eventually results in death because they can no longer breathe. About 20,000 new cases are diagnosed each year.

Their assessment appears throughout various portions of a 73-page document that was released on Friday in advance of a meeting next week of FDA experts. The panel will review clinical trial data for the drug, which is known as eteplirsen, and may be asked to vote on whether to recommend the agency should approve the treatment. Wall Street reacted by sending Sarepta stock plummeting more than 50 percent in midday trading.

“The news is grim,” wrote Needham analyst Chad Messer in an investor note.


Among the conclusions, FDA staffers wrote that data suggesting the drug helps produce higher levels of a needed protein called dystrophin “appear unreliable.” Without dystrophin, muscle fibers degenerate and voluntary movement becomes impossible. “Considerable doubt remains about how much, or perhaps even whether, dystrophin levels were increased by eteplirsen,” they wrote.

The FDA reviewers also expressed “significant concerns” about whether “valid conclusions” can be drawn from the results of a six-minute walking test, which is a standard measure of physical function. Among other data, Sarepta hopes the results will convince the FDA to grant accelerated approval, a process the agency can use to approve drugs for unmet medical needs based on surrogate markers.


But one key hurdle that Sarepta faces is that its data is based on just one trial of just 12 boys, a very small sample size. “Although FDA is prepared to be flexible with respect to a devastating illness with no treatment options, we cannot approve drugs for which substantial evidence of effectiveness has not been established,” the FDA reviewers wrote.

The sentiment provides a clear window into agency thinking about drugs for DMD, which has become a flashpoint in the heated debate about the extent to which the FDA is responsive to patient needs. A growing chorus of advocacy groups argues the agency should allow patients and families to decide for themselves if a drug for an unmet medical need is worth any potential risks.

This wider issue has engulfed the FDA, especially after Congress passed a law four years ago requiring the agency to become more responsive to patients. Even so, the agency remains under attack and the DMD drugs are being seen as a litmus test, especially after FDA officials encouraged DMD advocacy groups to draft guidelines for drug development, which served as a blueprint for the agency.

Just yesterday, though, the FDA rejected a DMD drug from BioMarin Pharmaceutical, which will now have to generate new late-stage clinical trial data in hopes of winning marketing approval. The medicine failed a late-stage study, but the drug maker tried to convince the FDA that a subset of data indicated its treatment was useful. Despite the shortcomings, families lobbied the FDA vociferously for approval.

“As it did with BioMarin’s [drug,] the FDA is making clear that unmet need and patient advocacy do not substitute for substantial evidence of efficacy,” said Michael McCaughan of Prevision Policy, a health care consulting firm. “Unfortunately, neither of these [marketing] applications comes close to meeting that standard.”

Not surprisingly, parents are upset at the back-to-back statements coming from the FDA this week about the two DMD drugs. Dozens, perhaps, hundreds of families — some with children who have DMD and get around in wheelchairs — are planning to attend the FDA panel meeting next week.

“The FDA is continuously looking for excuses to say no, [rather] than reasons to say yes to these drugs,” said Jenn McNary, who has two sons with DMD, one of whom was enrolled in the Sarepta clinical trial. She also works for the Jett Foundation, a nonprofit devoted to DMD awareness and research. “I’m just very angry.”

As a result, the meeting may turn into a showdown. One Wall Street analyst believes the FDA may yet approve the Sarepta drug, especially since the agency has now rejected the BioMarin medication and DMD patients will not have any options.

“The FDA is going to have a hard time saying no,” said Stephen Brozak, who heads WBB Securities. “But either way, this is going to be the mother of all battles in FDA land.”

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