Sarepta Fails Confirmatory Trial for DMD Therapy, Still Eyes Label Expansion

Pictured: Boy in a wheelchair looking out the wind

Pictured: Boy in a wheelchair looking out the wind

Despite failing to hit the primary endpoint in the Phase III EMBARK study, the company plans to file for a label expansion for its Duchenne muscular dystrophy gene therapy Elevidys.

Pictured: Boy in a wheelchair looking out a window/iStock, Prostock-Studio

Sarepta Therapeutics on Monday posted topline data from the Phase III EMBARK study, showing that its Duchenne muscular dystrophy gene therapy Elevidys (delandistrogene moxeparvovec-rokl) fell short of its primary efficacy endpoint, unable to significantly improve functional mobility versus placebo.

Nonetheless, based on what the company calls “robust evidence” of “clinically meaningful treatment benefit” across all EMBARK’s pre-specified key functional secondary endpoints, Sarepta will push through with filing for a label expansion for Elevidys.

“We have shared the EMBARK topline results with FDA leadership and 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,” Sarepta CEO Doug Ingram said in a statement.

In EMBARK, a randomized, two-part crossover and placebo-controlled study, Sarepta dosed 125 Duchenne muscular dystrophy (DMD) patients aged four to seven years with either Elevidys or a matching placebo. The trial’s primary endpoint was functional motor abilities, as measured by scores on the North Star Ambulatory Assessment (NSAA) 52 weeks after treatment.

Patients treated with the gene therapy saw a 2.6-point improvement on the NSAA, while scores of placebo comparators increased by 1.9 points. The between-group difference of 0.65 points was not statistically significant, with a p-value of 0.24, according to Sarepta’s announcement.

Despite failing the primary endpoint, Sarepta touted the secondary efficacy findings for Elevidys, which significantly outperformed placebo—in the overall study sample and across all age subgroups—in terms of time to rise and the 10-meter walk test. Elevidys also demonstrated treatment benefit in other timed functional endpoints, including stride velocity and time to ascend four steps.

“Passing five seconds on time to rise is the strongest predictor of early loss of ambulation and in EMBARK, Elevidys reduced those odds over 52 weeks by greater than 90%,” Ingram said, adding that these data “support the conclusion that Elevidys modifies the trajectory of Duchenne and benefits patients across age groups.”

Elevidys is a single-dose and intravenously infused gene transfer therapy designed to target the underlying cause of DMD. It works by using an adeno-associated virus vector to deliver a gene that encodes for the dystrophin protein. In DMD, the dystrophin gene is mutated, which leads to the hallmark progressive muscle weakness and wasting.

The FDA granted Elevidys accelerated approval in June 2023, allowing the therapy to be used in ambulatory patients aged four to five years. Sarepta ran the EMBARK study as a confirmatory trial for Elevidys’ full approval as well as to expand its label to include a broader pediatric patient population. At the time, however, some analysts raised concerns that data from EMBARK might not be enough to secure this expansion.

Elevidys is being developed and commercialized in partnership with Roche, which is responsible for marketing the treatment outside the U.S.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

Tristan is an independent science writer based in Metro Manila, with more than eight years of experience writing about medicine, biotech and science. He can be reached at, or on LinkedIn.