LB: Pooled Safety Analysis from Phase 1 to Phase 3 Clinical Trials of Delandistrogene Moxeparvovec in Duchenne Muscular Dystrophy

Topic:

Clinical Trials

Poster Number: 478 LBT

Author(s):

Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Craig McDonald, MD, University of California (UC) Davis Medical Center, Eugenio M. Mercuri, MD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Rome, Italy, Francesco Muntoni, MD, Dubowitz Neuromuscular Centre, UCL and Great Ormond Street Hospital Trust, London, UK, Craig M. Zaidman, MD, Department of Neurology, Washington University in St Louis, St Louis, MO, USA, Vannary Chhay, PharmD, RPh, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Matthew Furgerson, PhD, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Jim Jin, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Alexander P. Murphy, MBChB, PhD, Roche Products Ltd, Welwyn Garden City, UK, Mark Vivien, PharmD, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Marianne Gerber, MD, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Jerry R. Mendell, MD, Sarepta Therapeutics, Inc., Cambridge, MA, USA

Background: Delandistrogene moxeparvovec, an rAAVrh74 vector-based gene therapy approved in the US and other select countries, delivers a transgene encoding an engineered, functional dystrophin that slows Duchenne muscular dystrophy (DMD) disease progression in ambulatory patients. Pooled delandistrogene moxeparvovec safety outcomes across clinical trials with up to 7.5 years’ follow-up are presented.

Methods: Data were collected from Study 101 (NCT03375164), Study 102 (NCT03769116), ENDEAVOR Cohorts 1–7 (NCT04626674), EMBARK (NCT05096221), and ENVOL Cohorts A and B (NCT06128564) as of 13 October 2025 (latest cutoff).

Results: The pooled analysis included 227 ambulatory (96.2%) and nine non-ambulatory (3.8%) patients (mean [range] age: 6.6 [2.0–24.7] years). Most treatment-related treatment-emergent adverse events (TR-TEAEs) first appeared within the first 90 days post-infusion and resolved spontaneously or with appropriate intervention. The most frequently reported (≥15% of patients) TR-TEAEs were vomiting (58.5%), nausea (36.0%), decreased appetite (28.8%), glutamate dehydrogenase increased (20.3%), and gamma-glutamyl transferase increased (15.3%). The treatment-related serious AEs observed during the first 60 days were liver injury (including gamma-glutamyl transferase increased, hepatic enzyme increased, hepatotoxicity, hypertransaminasaemia, liver injury, and transaminases increased) (n=13 patients, 5.5%), vomiting (n=5, 2.1%), pyrexia (n=3, 1.3%), myocarditis (n=2, 0.8%), rhabdomyolysis (n=2, 0.8%), and nausea (n=1, 0.4%). There have not been any reported clinically significant AEs related to complement activation in clinical studies with delandistrogene moxeparvovec. To date, there have been two treatment-related deaths due to acute liver failure approximately 3 months post‑infusion in non-ambulatory patients (one in the ENVISION trial and one in the commercial setting) at 15 and 16 years of age.

Conclusions: Overall, the safety and tolerability profile of delandistrogene moxeparvovec in this pooled analysis was manageable with appropriate monitoring and treatment of AEs, which typically occur within 90 days post-infusion.