A high-profile clinical trial testing Sarepta Therapeutics’ new gene therapy for Duchenne muscular dystrophy failed to meet its main goal, the biotechnology company said late Monday in an update that calls into question the treatment’s future.
However, Sarepta, which has a history of back-and-forth interactions with regulators, claimed additional data from the study show a consistent benefit to treatment. The company has shared the results with the Food and Drug Administration and plans to ask the agency to expand its clearance of the therapy, which Sarepta sells as Elevidys.
The news comes four months after the FDA granted Elevidys accelerated approval in 4- and 5-year-old boys with Duchenne, an inherited disease that progressively weakens muscles. Sarepta’s trial, called EMBARK, was meant to confirm that approval by showing increased levels of a muscle-protecting protein translate to more definitive health benefits.
On the study’s main measure, a functional scale known as the North Star Ambulatory Assessment, trial participants treated with Elevidys improved by 2.6 points, compared to 1.9 points among those given placebo. The difference was not statistically significant, Sarepta said.
But on other measures, such as how quickly participants could rise or walk 10 meters, Elevidys appeared to help participants improve. Sarepta plans to share full study results at an upcoming medical meeting and publish them in a medical journal.
Typically, the FDA does not consider data on secondary study goals to be positive if the trial misses its primary endpoint. But it has taken a more flexible approach when diseases are severe, like Duchenne, and when patients have few good treatment options.
Doug Ingram, Sarepta’s CEO, told investors on a call Monday afternoon that the company views its data as showing Elevidys can change Duchenne’s course.
"Our goal is to expand the label to cover all amenable Duchenne patients without regard to age or ambulatory status,” said Ingram. “FDA leadership has also confirmed their goal of moving swiftly to review this new data and conclude its review on the label expansion, hence we will be moving rapidly to make a formal submission.”
Ingram added that Sarepta has already met with senior FDA officials, including Center for Biologics Evaluation and Resaerch Director Peter Marks, who previously intervened in the agency’s review of Elevidys, according to reporting from Stat.
“It was a very productive, very positive meeting,” Ingram said. “I want to be very clear: we still have a submission and a review to go through but I was very encouraged by the discussions with the agency.”
Sarepta studied Elevidys in boys with Duchenne between the ages of 4 and 7, and initially asked for approval in ambulatory indidviduals. But the data the biotech had marshalled in support were mixed and the agency ultimately decided on a compromise approval in only 4- and 5-year olds, for whom results appeared more positive.
EMBARK, which enrolled 125 boys with Duchenne, was therefore viewed as a way to expand Elevidys’ use to the older children who couldn’t access the treatment because of their age. As Duchenne is progressive, older boys tend to have lost more function that Elevidys would be unlikely to restore.
Data shared by Sarepta Monday showed that on the NSAA scale the younger boys enrolled in the study appeared to do better than those who were older.
While about a third of trial participants experienced a side effect judged to be related to treatment, few were serious, Sarepta said. No one in the study discontinued and there were no deaths.
Roche, which paid Sarepta more than $1 billion to collaborate on Elevidys, took a more muted approach in its statement on the trial.
“High unmet need remains in Duchenne and we are encouraged by the consistent and meaningful results seen in all key secondary functional endpoints for Elevidys,” said Roche Chief Medical Officer Levi Garraway, in a statement. “We will work to further analyse the Embark results and consult with health authorities as quickly as possible.”
Under the companies’ alliance, Roche is responsible for regulatory reviews outside of the U.S., while Sarepta is in charge of discussions with the FDA.
Sarepta is slated to report earnings for the third quarter on Wednesday. The biotech sells three other drugs for Duchenne, but their use is limited to certain groups of patients.
Unlike those drugs, Elevidys is meant to be a one-time treatment that replaces the gene that’s damaged in people with Duchenne. However, because of the size of that gene and how the therapy is delivered, Sarepta had to engineer a “mini” version of the gene, which produces a shortened form of the crucial dystrophin protein.
Shares in Sarepta fell by more than 40% in Tuesday morning trading, erasing billions of dollars in market value
Gwendolyn Wu contributed reporting.
Editor’s note: This story has been updated to include comments from Sarepta Therapeutics CEO Doug Ingram, as well as the stock market reaction Tuesday.