On May 16, 2025, Sarepta Therapeutics announced positive data for delandistrogene moxeparvovec-rokl (ELEVIDYS), the only FDA approved gene therapy for patients with Duchenne muscular dystrophy (DMD), from part 2 of the EMBARK study. The data were presented at the 28th annual meeting of the American Society of Gene & Cell Therapy (ASGCT) Conference.¹

Background on delandistrogene moxeparvovec-rokl

According to a press release from Sarepta, delandistrogene moxeparvovec-rokl is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of DMD. The therapy was first approved by the FDA on June 22, 2023, for individuals with a confirmed mutation in the DMD gene aged 4 to 5 years.² Then, on June 20, 2024, the federal agency approved an expanded label to include patients aged 4 years and older.³

Data presented at ASGCT

The EMARK study, a phase 3, randomized, 2-part crossover, placebo-controlled study of delandistrogene moxeparvovec-rokl among DMD patients aged 4 to 7 years, had a primary endpoint of change in baseline in North Star Ambulatory Assessment (NSAA) after 1 year following treatment. Part 1 of the trial included 125 patients aged 4 years and up to younger than 8 years, who were randomized by age or NSAA Total Score at screening (>16 to <29) and received either 1.33 x10¹⁴ vg/kg of delandistrogene moxeparvovec-rokl or placebo with a follow-up period for 52 weeks.¹

Part 2 featured a crossover, meaning patients who were treated with placebo in part 1 of the study received delandistrogene moxeparvovec-rokl in part 2, and those treated with the gene therapy in part 1 switched to placebo in part 2. Each group was followed-up for 52 weeks, and all participants were blinded in both parts of the study.

Part 2 included 14 patients who received placebo in part 1 who were aged 8 to 9 years at crossover. One year after treatment, there were between-group differences (least square means) across all key endpoints that were statistically significant, according to Sarepta. These data included, compared to a well-matched external cohort:

• 4.75 points (P = 0.0026) on NSAA
• 6.87 seconds in time-to-rise (TTR) from the floor (P = 0.0010)
• 4.76 seconds in 10-meter walk/run (10MWR) (P = 0.0097)

"The latest data from the EMBARK study highlighting motor function improvements in 8- and 9-year-old boys is encouraging and adds to the growing body of evidence supporting [delandistrogene moxeparvovec-rokl]," said Aravindhan Veerapandiyan, MD, associate professor of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital. "What stands out is that these patients were treated at an age when motor decline is typically expected in those with Duchenne. Yet, those who received [delandistrogene moxeparvovec-rokl] demonstrated statistically significant and clinically meaningful functional improvements compared to external controls," said Veerapandiyan in a statement.

Results at 2 years post-treatment against data from the external group of untreated individuals with DMD revealed that those treated with the approved gene therapy had better outcomes in multiple motor function measures. There were no new safety signals observed in the study across the 2-year period. Additionally, in a subset of patients (n = 16), micro-dystrophin expression and sarcolemmal localization was sustained from Week 12 to Week 64.

“This has been a significant year for our neuromuscular portfolio, with multiple, ongoing analyses and longer-term data on efficacy and safety presented for [delandistrogene moxeparvovec-rokl],” said Louise Rodino-Klapac, PhD, chief scientific officer and head of research and development, Sarepta Therapeutics, in a press release. “Building on the topline EMBARK Part 2 data from earlier this year, we’re committed to sharing ongoing analyses as fast as possible. The one-year results of patients treated with [delandistrogene moxeparvovec-rokl] at 8 to 9 years old provide evidence that those treated with gene therapy outperform those who don’t receive it at a critical point when more dramatic functional decline is expected.”

References:

1. Sarepta Therapeutics Presents Data at the American Society of Gene & Cell Therapy Conference, Including Statistically Significant Functional Outcomes for 8- and 9-Year-Old Patients in New Data Analysis of EMBARK Part 2. Sarepta Therapeutics. Press release. May 16, 2025. Accessed May 16, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-presents-data-american-society-gene-cell

2. Fitch, J. FDA approves first gene therapy to treat pediatric patients with Duchenne muscular dystrophy. Contemporary Pediatrics. June 22, 2023. Accessed May 16, 2025. https://www.contemporarypediatrics.com/view/fda-approves-first-gene-therapy-to-treat-pediatric-patients-with-duchenne-muscular-dystrophy

3. Fitch, J. Expanded indication sees DMD treatment approved for patients 4 years and up. Contemporary Pediatrics. June 21, 2024. Accessed May 16, 2025. https://www.contemporarypediatrics.com/view/expanded-indication-sees-dmd-treatment-approved-for-patients-4-years-and-up