RARE Daily

Sarepta’s Topline Results from Confirmatory DMD Gene Therapy Study Miss Primary Endpoint

October 31, 2023

Rare Daily Staff

Although Sarepta Therapeutics reported topline results from a confirmatory study of Elevidys in children between the ages of 4 through 7 years with Duchenne muscular dystrophy that missed the primary endpoint, the company said it will still seek broader approval in the United States.

Shares of Sarepta sank 40 percent on the news.

The U.S. Food and Drug Administration granted accelerated approval to the gene therapy earlier in the year.

“The results of EMBARK, our double-blind, placebo-controlled trial, support the conclusion that Elevidys modifies the trajectory of Duchenne and benefits patients across age groups living with this ferociously degenerative disease. The results favored Elevidys across all endpoints in the study, including achieving statistical significance on all pre-specified key secondary endpoints and in each age subgroup of the key secondary endpoints. Indeed, passing 5 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 percent,” said Doug Ingram, president and CEO of Sarepta. “Based on the EMBARK results, we intend to move swiftly to request an update to expand the labeled indication to treat all patients. Importantly, 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.”

EMBARK is a global, randomized, double-blind, placebo-controlled, phase 3 clinical study of Elevidys gene therapy in patients with Duchenne muscular dystrophy between the ages of 4 through 7 years. In the study, Elevidys-treated patients improved 2.6 points on their North Star Ambulatory Assessment (NSAA) total score 52 weeks after treatment compared to 1.9 points in placebo-treated patients. The difference of 0.65-points between treated and placebo groups did not reach statistical significance.

All key pre-specified functional secondary endpoints demonstrated robust evidence for a clinically meaningful treatment benefit that was consistent across age groups in Elevidys -treated patients compared to placebo at 52 weeks, including time to rise and 10-meter walk test (p=0.0048), demonstrated evidence of a clinically meaningful treatment benefit that was similar in magnitude and statistical significance across all age groups.

There were no new safety signals in the EMBARK study, reinforcing the favorable and manageable safety profile observed with ELEVIDYS to date. The most common treatment-related adverse events were gastrointestinal events (vomiting, nausea, and decreased appetite) and pyrexia. Seven participants experienced a treatment-related serious adverse event (SAE) and there were no clinically meaningful changes observed in SAEs associated with known risks of ELEVIDYS.

As part of a collaboration agreement signed in 2019 with Roche, Sarepta is responsible for regulatory approval and commercialization of Elevidys in the U.S., as well as manufacturing. Roche is responsible for regulatory approvals and bringing Elevidys to patients across the rest of the world.

Photo: Doug Ingram, CEO of Sarepta Therapeutics


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