EMBARK Data Support Delandistrogene Moxeparvovec for DMD Across All Study End Points


Over a 52-week treatment period, the gene therapy demonstrated robust evidence for a clinically meaningful benefit, including across several prespecified functional secondary end points vs placebo.

NeurologyLive® originally published this article. This version has been lightly edited.

Douglas S. Ingram, JD | Image Credit: Sarepta Therapeutics

Douglas S. Ingram, JD

Image Credit: Sarepta Therapeutics

Months after the FDA approved Sarepta Therapeutics’ gene therapy delandistrogene moxeparvovec (Elevidys, Sarepta Therapeutics) for the treatment of ambulatory patients with Duchenne muscular dystrophy (DMD), the company announced topline data from the phase 3 EMBARK study (NCT05096221), a trial aimed to reinforce the agent’s efficacy. Full results from EMBARK are expected to be shared at a future medical meeting and publication will be pursued in a medical journal.1

Data from the 2-part, crossover, placebo-controlled study showed that patients with DMD aged 4 to 7 years improved 2.6 points on the North Star Ambulatory Assessment (NSAA) total score, the primary end point, 52 weeks after treatment started. In comparison, those on placebo improved 1.9 points, a difference that was not considered statistically significant between groups (P = .24). In addition, treatment with the gene therapy resulted in robust changes on all key prespecified functional secondary end points over the treatment period.

"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," Doug Ingram, president and CEO of Sarepta, said in a statement.1 "The results favored Elevidys across all end points in the study, including achieving statistical significance on all prespecified key secondary end points and in each age subgroup of the key secondary end points. 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%."

In EMBARK, eligible patients received a single dose of the genetic treatment during either part 1 or part 2 of the study. In part 1, participants (n = 125) were randomized according to age (≥ 4 to < 8 years) or NSAA total score at screening (> 16 or < 29) and received either 1.33 x 1014 vg/kg of treatment or placebo, with a follow-up period of 52 weeks. Following part 1, patients from both groups crossed over to the opposite treatment for part 2, where they were followed for 52 weeks. All patients remain blinded.1

Across secondary end points, investigators recorded a least square mean (LSM) difference of –0.64 (P = .0025) in change on time to rise (TTR) for those who received treatment vs placebo. The effects of the agent were more pronounced among treated patients aged 6 to 7 years (LSM change vs placebo, –0.78; P = .0291) than among patients aged 4 to 5 years (LSM change vs placebo, –0.50; P = .0177). Similarly, the treatment resulted in clinically meaningful effects on the 10-meter walk test (LSM change vs placebo, –0.42; P = .0048), with greater effects observed among those aged 6 to 7 years (LSM change vs placebo, –0.52; P = .0363) than those aged 4 to 5 years (LSM change vs placebo, ­–0.33; P = .0319).

"Based on the EMBARK results, we intend to move swiftly to request an update to expand the labeled indication to treat all patients," Ingram said.1 "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."

According to the update, there were no new observed safety signals in the trial, with a safety profile that was consistent with delandistrogene moxeparvovec to date. The most common treatment-related adverse events (AEs) were gastrointestinal events, including vomiting, nausea, and decreased appetite, as well as pyrexia. Seven participants (11.1%) experienced a treatment-related serious AE and there were no clinically meaningful changes observed in these AEs associated with the known treatment risks.

Delandistrogene moxeparvovec was approved by the FDA earlier this year as the first gene therapy for patients with DMD with a confirmed mutation in the DMD gene.2 An adeno-associated virus vector-based gene therapy, it was approved based on data from several studies: the phase 1/2 SRP-9001-101 (NCT03375164), the phase 2 SRP-9001-102 study (NCT03769116), and the phase 1 ENDEAVOR study (SRP-9001-103; NCT04626674). The medication is indicated for ambulatory pediatric patients aged 4 to 5 years with DMD and is contraindicated for those with any deletion in exon 8 and/or exon 9 in the DMD gene.

Craig McDonald, MD | Image Credit: UC Davis Health

Craig McDonald, MD

Image Credit: UC Davis Health

"The strong prognostic power of time to rise, and the particular importance of the 5-second milestone in predicting functional decline and future loss of ambulation, is clearly demonstrated in natural history. In EMBARK, the reduction in patients progressing past this milestone when treated with Elevidys is highly clinically relevant," Craig McDonald, MD, professor and chair of the UC Davis Health Department of Physical Medicine and Rehabilitation, and an investigator of EMBARK, said in a statement.1 "The consistency of the positive effect across all timed function tests and age groups provides evidence of a meaningful treatment effect. In addition, it is important to note that this is the first clinical trial in the history of DMD trials to show a statistically significant and meaningful improvement on the novel measure of 95th centile stride velocity derived from an objective community wearable activity monitor."


1. Sarepta Therapeutics announces topline results from EMBARK, a global pivotal study of ELEVIDYS gene therapy for Duchenne muscular dystrophy. News release. Sarepta Therapeutics. October 30, 2023. Accessed October 31, 2023.

2. Sarepta Therapeutics announces FDA approval of Elevidys, the first gene therapy to treat Duchenne muscular dystrophy. News release. Business Wire. June 22, 2023. Accessed October 31, 2023.

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