Sarepta's Elevidys fails on primary endpoint, but executives see path to wider DMD approval anyway

After Sarepta Therapeutics overcame several regulatory hurdles to finally win FDA approval for its Duchenne muscular dystrophy (DMD) gene therapy Elevidys, the company now faces the prospect of more FDA scrutiny because a pivotal study on the drug has failed on the primary endpoint.

The endpoint, a measure of motor function called the North Star Ambulatory Assessment (NSAA), failed to reach statistical significance in the phase 3 EMBARK study, Sarepta said in a Monday release.

Despite this result, Sarepta Chief Scientific Officer Louise Rodino-Klapac, Ph.D., touted "clinically meaningful" effects seen across the trial's secondary endpoints. Speaking on a Monday conference call, Rodino-Klapac said Sarepta plans to file for a label expansion to treat "all DMD patients" and to convert the drug's accelerated approval into a traditional nod.

Sarepta CEO Doug Ingram said the study “met the standard" to show "evidence of effectiveness.” He added that the results show that the drug "alters" the course of disease in patients with DMD and that the company has had "encouraging" early discussions with the FDA about the data.

As the company proceeds with its regulatory interactions, Sarepta is planning for the "broadest possible label" from a supply and manufacturing perspective, Ingram added.

Despite Sarepta's optimism, investors saw things differently. The company's share price was down about 41% to $63.19 midday Tuesday.

In the study, investigators randomized a total of 125 DMD patients ages 4 to 7 to receive either Elevidys or placebo. After 52 weeks, researchers recorded patients' change in NSAA from baseline. Patients treated with the gene therapy experienced a 2.6-point increase in NSAA, compared with 1.9 for those on placebo. The result wasn't statistically significant.

The secondary endpoints included the change from baseline in a patient's time to rise from the floor and the change in a 10-meter walk or run time. Investigators also looked at the quantity of Elevidys dystrophin protein expression. Sarepta said these endpoints "demonstrated robust evidence for a clinically meaningful treatment benefit." 

On the time to rise from the floor, patients treated with the drug experienced a 0.64-second improvement versus placebo. On the 10-meter distance test, the drug was associated with a 0.42-second improvement versus placebo, Sarepta said.

Elevidys won an accelerated FDA approval back in June to treat ambulatory patients ages 4 to 5 years with a confirmed mutation in the DMD gene. Sarepta is charging $3.2 million for the one-time gene therapy.

Before the approval, an FDA advisory committee meeting resulted in a 8-6 vote in favor of the therapy’s risk-benefit profile. 

Elevidys and Sarepta traveled a long road to the accelerated approval that included clinical holds in 2018 and 2021.