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Dashing hopes of parents and investors, the US Food and Drug Administration on Thursday released documents suggesting the agency continues to have a highly unfavorable view of a drug used to combat Duchenne muscular dystrophy, a rare disease that causes muscles in boys to stop working and eventually results in death because they can no longer breathe.

In blunt language, agency staffers disputed the analysis and methodology behind crucial data that Sarepta Therapeutics used to bolster its case for approval of its drug, which is called eteplirsen. Notably, the FDA medical reviewers also made a point of rebuking the company for alleging earlier this year that the agency made “key inaccuracies” in a previous assessment.

The fate of the Sarepta drug has been closely watched as a litmus test for an intensifying struggle between the FDA and patient groups that want the agency to take a more expansive view toward approving medicines for unmet medical needs. In recent months, the FDA has rejected two other drugs for DMD, which afflicts about 13,000 children, mostly boys.


Now, though, it appears that it may be “three strikes” for the first crop of DMD treatments.

“Although FDA is prepared to be flexible with respect to a devastating illness with no treatment options, flexibility does not mean approving drugs for which substantial evidence of effectiveness has not been established,” the agency reviewers wrote in briefing documents. These were posted on the FDA website in advance of an advisory panel meeting scheduled to take place on Monday to review the drug.


Specifically, FDA reviewers questioned whether the drug could produce higher levels of a protein called dystrophin. Without this protein, muscle fibers degenerate and voluntary movement becomes impossible. The FDA also raised doubts about the veracity of a 12-patient clinical trial that Sarepta relied on to make its case, as well as the viability of six-minute walking tests that trial participants underwent.

The agency assessment prompted sharp reactions from investors and patient groups alike. Sarepta stock fell nearly 45 percent on heavy trading volume, to $10.85, after the agency documents were released. Wall Street analysts, meanwhile, offered gloomy forecasts. The tone of the FDA review is “very critical, very unconvinced,” Cowen analyst Ritu Baral wrote in an investor note.

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Underscoring the controversy surrounding this drug, an FDA heavyweight — Janet Woodcock, who heads the agency division that reviews drugs — will make a presentation at the Monday advisory panel. She is expected to discuss the clinical trial design issues surrounding the Sarepta drug, according to Leerink analyst Joseph Schwartz.

To some, this may appear to be a defensive move, given that the agency has been under pressure to use the accelerated approval process to greenlight the Sarepta drug. The agency can take this approach to consider medicines that treat serious conditions and satisfy unmet medical needs based on a surrogate endpoint. In this instance, Sarepta argued the production of dytrophin was such an endpoint.

Last month, for instance, more than three dozen medical experts circulated a letter urging the agency to approve the drug. They also criticized the FDA for its earlier assessment, which was released prior to a January advisory panel meeting to review the drug that had been postponed. Several of those academics, however, also have various ties to Sarepta.

Their letter did not go unnoticed. In the briefing documents just released, the agency noted that Sarepta was “strongly encouraged” to conduct a randomized, placebo‐controlled trial to assess its drug. But after considering concerns from parents and academics about the ethics of running such a trial, the agency relented and “expressed willingness” to consider Sarepta’s approach.

The upcoming meeting on Monday is likely, of course, to hinge on the many doubts raised by the FDA. Of course, the agency remains under political pressure. Two months ago, more than 100 members of Congress wrote FDA officials and urged them to approve the drug. This sort of backdrop is one reason parents continue to hold out hope.

“The FDA’s initial reaction is just that – an initial response — and there is evidence still to be presented to the advisory committee,” said Debra Miller, who heads CureDuchenne, an advocacy group that raises money to invest in drug makers that are developing products to combat DMD. “While we understand the FDA needs to make sure drugs are safe and effective, we also know the consequence of inaction for those with Duchenne. We are hopeful for accelerated approval.”

  • The need is indeed great, BAK, but for something that works. I found a bit ago that the price is estimated at $265000/year per patient. Given that the pries are pure fantasy, it’s what the company would like to charge. If only 5,000 out of the 13,000 get the drug at that price (just using the numbers out there), the cost would be $1.3 Billion USD per year. That’s a … high number to essentially run a Phase 4 (well, for this, decent Phase 3) clinical trial.

  • This is an awful thing for any parent to have to deal with, I can’t imagine the agony. I am reminded of another study that had a sample size of 12 children. The results are still being felt. That was the study by Andrew Wakefield, who published the conclusion that MMR Vaccine caused autism. There needs to be a larger sample size and long-term follow up.

    • Your reply frames the dialectic – because this is a BAD disease, any kind of ‘cure’ must be good. Even if it isn’t really a cure and is back-channel supported by people with a profit driver,

  • I don’t know how todays’ meeting will turn out but IMHO the driver is money. Even if the FDA replaces statistics with anecdotal results, however narrowly defined, I forsee a high priced med being prescribed at physician discretion/ coercion for any/every child who has this malady. Hope is pricele$$ but drug$ are not – this is a push to make FDA unlock the money spout. If the price is set at $100/month, I will profoundly apologize.

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