After Drug Trial Fizzles, Sarepta Still Seeks Broad Approval

Robert Langreth and Gerry Smith, Bloomberg News, October 31, 2023

Normally when a drug fails to show a clear effect in a final-stage trial, the company developing it goes back to the drawing board. But not Sarepta Therapeutics Inc.

Late Monday, the company said a trial of its $3.2 million gene therapy for Duchenne muscular dystrophy failed to clearly slow the disease in a year-long trial of 125 young kids with the
progressive muscle-wasting disease. The company’s stock declined 37% Tuesday, wiping out $3.76 billion in market value.

But Sarepta said that secondary measures of patients’ movement in the trial were positive, and it plans to go ahead and file with US regulators for expanded, full approval. Although the trial missed it main goal, the therapy’s benefits are evidenced “by effects on key secondary endpoints when compared to the placebo group,” a spokesperson said, saying that more trials are unnecessary.


Sarepta’s gene therapy was cleared in June via accelerated approval, a regulatory shortcut designed to get drugs for devastating diseases to market quickly, based on preliminary
data, before definitive trials are complete.


It got its first drug approved in 2016 amid controversy, and now has four drugs on the market for Duchenne muscular dystrophy. All four have been approved through the accelerated pathway, and not one has been unambiguously proven to slow the disease.

That’s why the new study was so significant — it was the first time Sarepta completed a confirmatory trial for any of its approved drugs. In it, kids ages 4 to 7 got either the gene
therapy or a placebo. After 52 weeks, those who got the therapy did no better on an overall measure of disease progression than those who got sham treatment.


The drug now has accelerated approval for 4- and 5-year- olds with DMD, and based on the new results, Sarepta hopes to convince the Food and Drug Administration to expand the approval
to 6- and 7-year-olds. The confusing results force the FDA into making a tough choice. It could do anything from rescinding the current approval, to giving it full approval for a broader age
group, to something in between.

‘Not Even Close’

“It would be ridiculous if FDA gave full approval based on this,” said Diana Zuckerman, president of the National Center for Health Research, a think tank that has been critical of FDA’s accelerated approval standards. The primary result “is not even close” to showing a statistical difference, she said.

The most likely scenario is that the drug remains on the market with accelerated approval, Zuckerman said, but doctors will be less likely to recommend it to patients given the less-than-stellar trial results.


Whatever happens, the controversy over Sarepta’s accelerated approval drugs is likely to continue for years.


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