DMD Gene Therapy Shows Clinical Benefits in 8- and 9-Year-Old Patients

Patients with Duchenne muscular dystrophy (DMD) aged 8 and 9 years experienced significant functional benefits with delandistrogene moxeparvovec-rokl (Elevidys; Sarepta Therapeutics) in part 2 of the EMBARK study (NCT05096221), according to recently presented data.1 

The findings, presented during the 28th American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, support the clinical benefits of delandistrogene moxeparvovec in patients with DMD. Later childhood is when muscle weakness typically progresses for patients with DMD, with symptoms appearing as early as 2 to 4 years.2

An analysis of outcomes from part 2 of the EMBARK trial included 14 patients who had received a placebo in part 1 of the study and were aged 8 to 9 years at crossover. | Image Credit: RFBSIP - stock.adobe.com

"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]," Aravindhan Veerapandiyan, MD, associate professor of pediatrics at the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, said in a press release.1 "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] demonstrated statistically significant and clinically meaningful functional improvements compared to external controls."

An analysis of outcomes from part 2 of the EMBARK trial included 14 patients who had received a placebo in part 1 of the study and were aged 8 to 9 years at crossover. These patients showed statistically significant between-group differences compared with a well-matched external control group based on least square means calculations.

At 1 year post treatment, there was a 4.75-point between-group difference in North Star Ambulatory Assessment (NSAA) scores (P = .0026), a 6.87-second difference in time to rise from the floor (P = .0010), and a 4.76-second difference in 10-meter walk/run (P = .0097).

The results are part of an ongoing analysis of part 2 of the EMBARK trial, with the data presented at ASCGT, including 2-year outcomes among 63 EMBARK participants who received gene therapy in part 1 of the study vs an external control group.3 At 2 years, patients who received gene therapy showed statistically significant and clinically meaningful benefits compared with external controls. In the overall cohort, the between-group difference in NSAA score was 2.88 points, the difference in time to rise was 2.06 seconds, and the difference in 10-meter walk/run was 1.36 seconds (all P < .01).

No new safety signals were seen in the 2-year analysis. Between weeks 52 and 104, 15 (23.8%) patients experienced a total of 34 treatment-related treatment-emergent adverse events (AEs). One patient experienced 2 treatment-related serious AEs of rhabdomyolysis, both of which resolved.

“This has been a significant year for our neuromuscular portfolio, with multiple, ongoing analyses and longer-term data on efficacy and safety presented for ELEVIDYS,” Louise Rodino-Klapac, PhD, chief scientific officer and head of research and development at Sarepta Therapeutics, said.1 “Building on the topline EMBARK Part 2 data from earlier this year, we’re committed to sharing ongoing analyses as fast as possible. The 1-year results of patients treated with ELEVIDYS 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.”

Delandistrogene moxeparvovec is an adeno-associated virus vector-based treatment approved for patients with DMD aged 4 years or older.4 Its initial approval came in June 2023 for patients with DMD aged 4 to 5 years, with an expanded approval in June 2024 including the treatment of all patients aged 4 years and older. Its approval for nonambulatory patients is under the FDA’s accelerated approval pathway.

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. News release. Sarepta Therapeutics. May 16, 2025. Accessed June 13, 2025.

2. Duchenne muscular dystrophy. Cleveland Clinic. July 25, 2022. Accessed June 13, 2025. https://my.clevelandclinic.org/health/diseases/23538-duchenne-muscular-dystrophy-dmd

3. Mendell J, Muntoni F, McDonald C, et al. Long-term functional outcomes and safety following delandistrogene moxeparvovec treatment in DMD: EMBARK 2-year results. Presented at: 28th American Society of Gene & Cell Therapy Annual Meeting; May 13-17, 2025; New Orleans, Louisiana. Abstract 355.

4. Shaw M. FDA grants 2 approvals to delandistrogene moxeparvovec for DMD. AJMC. June 20, 2024. Accessed May 23, 2025. https://www.ajmc.com/view/fda-grants-2-approvals-to-delandistrogene-moxeparvovec-for-dmd