LB: Delandistrogene Moxeparvovec in Duchenne Muscular Dystrophy: Functional and Safety Outcomes up to 3 Years Post-Infusion in the EMBARK Study

Topic:

Clinical Trials

Poster Number: 480 LBT

Author(s):

Jerry Mendell, MD, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Francesco Muntoni, MD, Dubowitz Neuromuscular Centre, UCL and Great Ormond Street Hospital Trust, London, UK, Craig McDonald, MD, University of California (UC) Davis Medical Center, Eugenio M. Mercuri, MD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Rome, Italy, Emma Ciafaloni, MD, FAAN, University of Rochester Medical Center, Rochester, NY, USA, Hirofumi Komaki, MD, PhD, Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, Carmen Leon Astudillo, MD, University of Florida, Andrés Nascimento, MD, Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu, Barcelona, Spain, Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Ulrike Schara-Schmidt, MD, Department of Pediatric Neurology, University of Duisburg-Essen, Essen, Germany, Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Craig M. Zaidman, MD, Department of Neurology, Washington University in St Louis, St Louis, MO, USA, Matthew Furgerson, PhD, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Jim Jin, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Mark Vivien, PharmD, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Damon R. Asher, PhD, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Alexander P. Murphy, MBChB, PhD, Roche Products Ltd, Welwyn Garden City, UK, Carol Reid, PhD, Roche Products Ltd, Welwyn Garden City, UK, Marianne Gerber, MD, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Carmen O. Torre, MSc, Roche Products Ltd, Welwyn Garden City, UK, Marianna Manfrini, MD, PhD, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Louise R. Rodino-Klapac, PhD, Sarepta Therapeutics, Inc., Cambridge, MA, USA

Background: Delandistrogene moxeparvovec, an rAAVrh74 vector-based gene therapy approved in the US and other select countries, slows Duchenne muscular dystrophy (DMD) progression in ambulatory patients. Three-year outcomes from patients treated in Part 1 of the EMBARK trial (NCT05096221) are presented.

Methods: In Part 1 (52 weeks), patients received delandistrogene moxeparvovec (single intravenous dose 1.33×1014 vg/kg) or placebo, with crossover in Part 2 (52 weeks). In the absence of a placebo control after crossover, 3-year functional outcomes (N=64) were compared with a matched external control (EC) cohort (N=143). Mixed effects models for repeated measures methods account for missing data. All P-values are nominal.

Results: Clinically meaningful, durable and nominally statistically significant efficacy was observed across all key motor function measures at 3 years post-infusion for Part 1-treated patients vs. EC, highlighting a widening treatment effect between 2 and 3 years (Mendell et al. Neurol Ther. 2026). Mean change from baseline to Year 3 and least-squares mean between-group differences were: North Star Ambulatory Assessment total score, 0.77 vs. –3.62 points (Δ4.39 points; P=0.0002); Time to Rise, 2.24 vs. 8.29 seconds (Δ–6.05 seconds; P<0.0001); 10-meter Walk/Run, 1.16 vs. 3.86 seconds (Δ–2.70 seconds; P=0.0039); Rise from Floor velocity, –0.04 vs. –0.10 rise/second (Δ0.06 rise/second; P=0.0004); 10-meter Walk/Run velocity, –0.08 vs. –0.43 meters/second (Δ0.36 meters/second; P=0.0003). Additional analyses will be presented. No new safety signals were observed between Years 2 and 3 (patients had rolled over into the long-term follow-up EXPEDITION study [Study 305, NCT05967351, cutoff date: 13 October 2025]).

Conclusions: At 3 years’ post-infusion, patients treated with delandistrogene moxeparvovec in EMBARK Part 1 continued to show nominally statistically significant functional benefits, with increasing divergence from natural history. Results demonstrate slowing of DMD progression and durability of treatment effect. Safety in this study was aligned with prior experience and manageable with appropriate monitoring.