Murky road ahead for Duchenne gene therapy as confirmatory trial misses main goal

When the first gene therapy for the rare, debilitating disease Duchenne muscular dystrophy was conditionally approved earlier this year, it was hailed as a seminal moment for patients and their families — an opportunity to try to slow the progression of a disease that robs kids of their ability to walk by their teen years, and can be fatal by age 30.

But the drug, called Elevidys, was only cleared by the US Food and Drug Administration for kids ages 4 and 5, based on the supporting evidence of how well it worked. Further study would be required to allow the drug to stay on the market, and to broaden its use to older children, who may be in more advanced stages of the disease.

Results from that study came Monday afternoon from drugmaker Sarepta Therapeutics, and they were anything but clear: The trial missed its main goal, a measure of how well kids can move, but was successful on a number of secondary measures.

The company’s chief executive, Doug Ingram, signaled optimism not just that the results would support keeping the drug on the market, but that they may enable its expanded use after all.

“We intend to move swiftly to request an update to expand the labeled indication to treat all patients,” Ingram said in a news release, noting Sarepta had shared the results with FDA leadership. “They have confirmed that, based on the totality of the evidence, they are open to such label expansion if supported by review of the data, and that they intend to proceed rapidly with consideration of the submission.”

Wall Street investors didn’t share Ingram’s optimism; Sarepta’s stock lost 40% of its value in trading Tuesday.

The FDA cleared Elevidys in June based on evidence showing it increases levels of a version of a protein called dystrophin, which acts like a shock absorber for muscles. It’s thought that increases in dystrophin should translate to clinical benefit, like being able to walk better.

Sarepta gave the one-time drug a price tag of $3.2 million, making it the second most-expensive medicine in the world. Other one-time gene therapies, which deliver copies of working genes to make up for ones that cause disease, often for very rare diseases, have also topped $3 million per patient. DMD affects one in 3,500 to 5,000 newborns, mostly boys because of the way it’s inherited, according to Johns Hopkins Medicine.

The primary goal of the confirmatory trial was improvement on a measure known as the North Star Ambulatory Assessment, a scale of how well kids can stand, walk and perform other movements.

The study, in kids ages 4 through 7, showed that a year after receiving the one-time treatment, those on the gene therapy improved by 2.6 points on the NSAA, while those in the placebo group improved by 1.9 points. The difference wasn’t statistically significant, meaning technically the study failed to meet its main goal.

Secondary measures, though, met the study’s goals and were statistically significant, like the time it takes kids to stand up, or to walk 10 meters. The company said no new safety issues emerged in the trial, which it called EMBARK.

Ingram told analysts and investors on a conference call Monday afternoon that the company is working on filing its application with the FDA now to expand the drug’s use to all ages and levels of walking ability.

“Our perspective is that the EMBARK results have met the standard for substantial evidence of effectiveness, confirming the mechanism of action of Elevidys, and showing that it alters the course of disease in Duchenne patients,” he said.

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