Delandistrogene Moxeparvovec Shows Long-Term Impacts at 3 and 5 Years in DMD

Patients with Duchenne muscular dystrophy (DMD) who received delandistrogene moxeparvovec (Elevidys; Sarepta Therapeutics) showed long-term disease stabilization or slowed disease progression at 3 and 5 years of follow-up in data presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Dallas, Texas.1,2

Delandistrogene moxeparvovec is an adeno-associated virus vector-based gene therapy approved for the treatment of ambulatory patients 4 years or older with a confirmed mutation in the DMD gene and for patients who are nonambulatory and have a confirmed mutation in the DMD gene under accelerated approval.3

Delandistrogene moxeparvovec is an adeno-associated virus vector-based gene therapy approved for the treatment of DMD. Image credit: natali_mis - stock.adobe.com

Pooled 3-year data from clinical trials of ambulatory patients treated with delandistrogene moxeparvovec (n = 50) showed long-term disease stabilization or slowing among treated patients vs propensity score–weighted external controls (n = 73) based on North Star Ambulatory Assessment (NSAA) total scores, time to rise (TTR) from floor, and 10-meter walk/run (10MWR).1 After propensity score weighting, the pooled treatment group and external controls had similar baseline covariate values.

In the treatment group, 3-year NSAA total score changes from baseline vs external controls were −2.55 vs −5.55 (P = .0003). Regarding TTR, the treatment group had a 3-year score change of 2.8, compared with 4.6 in the external control group (P < .0001). In the 10MWT, the treatment group’s 3-year score change was 1.4, compared with 1.8 in the control group (P = .059). Mixed models for repeated measures analyses showed similar results.

“These data suggest that delandistrogene moxeparvovec may have a clinically meaningful long-term impact on the disease course of DMD, modifying its trajectory relative to the natural history of the disease,“ the authors concluded.

Another study presented 5-year outcomes from Study 101 (NCT03375164), a phase 1/2a, single-dose, open-label clinical trial assessing delandistrogene moxeparvovec in ambulatory patients with DMD.2 The post hoc analysis included data from 4 patients treated with gene therapy put in context with a propensity score–weighted external control cohort (n = 17) and their natural history predictions.

The primary outcome in the trial was safety, with NSAA total scores and TTR from floor and 10MWR serving as key additional outcome measures. Baseline characteristics in the treatment and control cohorts were similar.

At 5 years, 75 adverse events (AEs) were reported, with most happening within 70 days of infusion. There were 18 reported treatment-related AEs, all of which were mild or moderate, and there were no severe AEs, clinically significant complement-mediated AEs, study discontinuations, or deaths. No new safety signals were reported after 70 days post treatment.

Regarding efficacy, patients treated with delandistrogene moxeparvovec showed a statistically significant and clinically meaningful difference in NSAA total score at 5 years vs the external control group. The treatment group also showed statistically significant and clinically meaningful differences in TTR from the floor and 10MWR time compared with the external control cohort.

Additionally, all treated patients remained ambulatory for the entire study duration. In the external control cohort, 4 patients lost ambulation between 8.4 and 11.6 years old, between 18 and 54 months post adjusted baseline.

“Long-term outcomes from this study support the biological role of functional dystrophin and indicate that delandistrogene moxeparvovec stabilizes or slows DMD disease progression with an increase in divergence from natural history over time,” the authors concluded.

References

1. Mendell J, Connolly AM, Day J, et al. 3-year functional outcomes of patients with Duchenne muscular dystrophy: pooled delandistrogene moxeparvovec clinical trial data vs external controls. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, TX. Poster 167.
2. Mendell JR, Sahenk Z, Lowes LP, et al. Five-year outcomes with delandistrogene moxeparvovec in patients with Duchenne muscular dystrophy (DMD): a phase 1/2a study. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, TX. Poster 118.
3. Elevidys. Prescribing information. Sarepta Therapeutics. Updated August 2024. https://www.elevidyshcp.com/pi