Neuropediatrics 2025; 56(S 01): S1-S24
DOI: 10.1055/s-0045-1812122
Neuromuscular Disorders

Long-Term Functional Outcomes, Safety, and Micro-Dystrophin Expression Following Delandistrogene Moxeparvovec Treatment in DMD: EMBARK 2-Year Results

Authors

  • I. Seelmann

    1   Uniklinik Essen, Essen, Germany
  • J. R. Mendell

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • F. Muntoni

    3   Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health and Institute of Neurology, University College London, & Great Ormond Street Hospital Trust, London, United Kingdom
  • C. M. McDonald

    4   UC Davis Health, Sacramento, United States
  • E. Mercuri

    5   Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
  • E. Ciafaloni

    6   University of Rochester Medical Center, Rochester, United States
  • H. Komaki

    7   Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan
  • C. Leon-Astudillo

    8   Department of Pediatrics, University of Florida, Gainesville, Florida, United States
  • A. Nascimento

    9   Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu, Fundacion Sant Joan de Déu, CIBERER, ISC III, Barcelona, Spain
  • C. Proud

    10   Children's Hospital of the King's Daughters, Norfolk, United States
  • U. Schara-Schmidt

    11   Department of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Clinic Essen, University of Duisburg-Essen, Essen, Germany
  • A. Veerapandiyan

    12   Department of Pediatrics, Division of Neurology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, United States
  • C. M. Zaidman

    13   Department of Neurology, Washington University in St Louis, St Louis, United States
  • M. Furgerson

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • K. Ding

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • P. Singh

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • R. Potter

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • D. R. Asher

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • A. P. Murphy

    14   Roche Products Ltd, Welwyn Garden City, United Kingdom
  • C. Reid

    14   Roche Products Ltd, Welwyn Garden City, United Kingdom
  • G. Hooper

    14   Roche Products Ltd, Welwyn Garden City, United Kingdom
  • C. O. Torre

    14   Roche Products Ltd, Welwyn Garden City, United Kingdom
  • M. Manfrini

    15   F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • J. S. Elkins

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • L. R. Rodino-Klapac

    2   Sarepta Therapeutics, Inc., Cambridge, United States
  • on behalf of the EMBARK Study Group

 

Background/Purpose: Delandistrogene moxeparvovec (rAAVrh74 vector-based gene therapy approved in the United States and other select countries) delivers a transgene encoding micro-dystrophin, an engineered, functional form of dystrophin that stabilizes/slows Duchenne muscular dystrophy (DMD) progression. EMBARK (NCT05096221), a Phase 3, randomized, double-blind, placebo-controlled, two-part study, assesses delandistrogene moxeparvovec in DMD.

Methods: EMBARK enrolled ambulatory males with DMD aged ≥4 to <8 years. In Part (P) 1 (52 weeks), patients received delandistrogene moxeparvovec (single intravenous dose 1.33×1014 vg/kg) or placebo. In P2, patients crossed over. Muscle biopsies were performed at weeks 12 and 64. Due to crossover, 2-year functional outcomes from P1-treated patients were compared with external controls (EC), matched using propensity-score-weighted analyses of baseline (BLN) prognostic factors of DMD progression.

Results: At 2 years, P1-treated patients (n = 63) demonstrated statistically significant and clinically meaningful functional benefit versus EC (n = 113–115, per assessment). Mean change from BLN (between-group difference): North Star Ambulatory assessment total score, 2.63 versus −0.25 points (2.88 points); Time to Rise, 0.65 versus 2.71 seconds (−2.06 seconds); 10-m walk/run, −0.04 versus 1.32 seconds (−1.36 seconds); all p < 0.01. Mean micro-dystrophin expression was sustained from weeks 12 (n = 17) to week 64 (n = 16; 34.29% versus 45.68%; western blot). Between week 52 and 104, 15 (23.8%) patients had 34 treatment-related (TR) treatment-emergent adverse events (AEs), including troponin-I increase (6.3%), proteinuria, and headache (3.2% each). One patient had two serious TRAEs of rhabdomyolysis; both resolved. Between BLN and W104, there were no TR deaths, study discontinuations due to AEs, or clinically significant complement-mediated AEs.

Conclusion: Two-year results indicate a favorable and durable effect of delandistrogene moxeparvovec on disease progression versus a well-matched EC. Safety was consistent with prior experience and manageable with appropriate monitoring.



Publikationsverlauf

Artikel online veröffentlicht:
26. September 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany