A new drug Eteplirsen for Duchenne muscular dystrophy

A new drug designed to slow the progression of Duchenne muscular dystrophy

A new drug designed to slow the progression of Duchenne muscular dystrophy

Eteplirsen uses an approach called exon skipping, intended to bypass the existing mutation and restore a gene’s ability to produce dystrophin. The goal is to create enough dystrophin production to transform Duchenne into a milder and more sustainable form of muscular dystrophy known as Becker.

In more than two years since Sarepta’s clinical trial began, the results have proved encouraging. Although many questions remain about how much dystrophin the drug actually helps to produce, the drug appears to have halted the decline for the boys in the trial, while showing no adverse side effects.

“It’s unequivocal. Since the day the kids were started on eteplirsen, they basically have never changed again. The natural history of the disease is to decline,” said Jerry Mendell, a pediatric expert at Nationwide Children’s Hospital in Columbus, Ohio, and the lead investigator on the Sarepta trial. “I see it as a game changer.”

Only about 13 percent of Duchenne patients have mutations that could benefit from eteplirsen, but Sarepta is developing similar drugs to treat boys with other exon deletions, along with clinical trials to test them.

The company said Monday that even as the FDA said its evaluators “remain skeptical” about the persuasiveness of some of Sarepta’s data, the agency encouraged it to push forward later this year with a larger “confirmatory” study that would provide more robust data about eteplirsen’s safety and effectiveness.

In the short term, that means as many as 100 additional patients — some older and some younger than the boys in the current trial — could gain access the drug prior to FDA approval. That study also is unlikely to have a placebo group, Garabedian said, meaning that every child enrolled will receive the drug.

“They know that the patients are waiting for this,” said Garabedian, who has said that the drug, if approved, could be among the most expensive ever in the United States.

Not everyone faults the FDA for taking so long to decide how to proceed on eteplirsen. Eric Hoffman, director of the Center for Genetic Medicine at Children’s National Medical Center and a longtime Duchenne researcher, said valid questions remain about eteplirsen’s dystrophin-producing abilities and how effective Sarepta’s drug really is over the long term.

“For accelerated approval, FDA wants a compelling case, and this is a case that’s been challenging to make compelling,” Hoffman said in an interview this month. “I’ve personally been very impressed with the FDA. They’ve been extremely interactive. . . . There’s every indication they are taking this extremely seriously.”

Even Louis Kunkel, a Harvard geneticist credited with discovering the gene behind Duchenne, said recently that he is “of mixed mind” on whether Sarepta has proved that eteplirsen is ready for FDA approval. On one hand, he said, the results are incredibly promising. On the other, Duchenne patients have faced many disappointments with therapies that seemed to offer hope but ultimately failed.

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