Safety and Efficacy of Delandistrogene Moxeparvovec versus Placebo in Duchenne Muscular Dystrophy (EMBARK): Pivotal Phase 3 Primary Results
Rattachement africain : de, us, gb, it, jp, es, ch. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Background/Purpose: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an adeno-associated viral vector-based gene transfer therapy, designed to compensate for absent functional dystrophin in DMD by delivering a transgene encoding engineered micro-dystrophin, which retains key functional wild-type dystrophin domains. As of September 2023, delandistrogene moxeparvovec is approved in the United States, UAE, and Qatar for the treatment of ambulatory pediatric patients aged 4 through 5 years with DMD with a confirmed DMD gene mutation. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: ambulatory patients aged ≥4 to <8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening; rAAVrh74 antibody titers <1:400; stable daily dose of oral corticosteroids for ≥12 weeks prescreening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33 × 10 14 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 ( n = 125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n = 63) versus placebo groups (1.9, n = 61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4–5 and 6–7 years; p < 0.05); stride velocity 95th centile and time to ascend 4-steps showed benefit that was similar in magnitude and significant in the overall population ( p < 0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusion: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory. Publication History Article published online: 08 October 2024 Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Safety and Efficacy of Delandistrogene Moxeparvovec versus Placebo in Duchenne Muscular Dystrophy (EMBARK): Pivotal Phase 3 Primary Results
- Date Crossref
- 01/10/2024
- Éditeur
- Georg Thieme Verlag KG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
University of Duisburg-Essen Department of Pediatric Neurology pays non établi dans la noticeUniversité ou école supérieure
-
Nationwide Children's Hospital pays non établi dans la noticeÉtablissement de santé
-
Great Ormond Street Hospital pays non établi dans la noticeÉtablissement de santé
-
NIHR Great Ormond Street Hospital Biomedical Research Centre pays non établi dans la noticeStructure de recherche
-
University College London pays non établi dans la noticeUniversité ou école supérieure
-
UC Davis Health pays non établi dans la noticeÉtablissement de santé
-
Istituti di Ricovero e Cura a Carattere Scientifico pays non établi dans la noticeÉtablissement de santé
-
University of Rochester Medicine pays non établi dans la noticeÉtablissement de santé
-
National Center of Neurology and Psychiatry pays non établi dans la noticeÉtablissement de santé
-
University of Florida Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
-
Hospital Sant Joan de Déu Barcelona Neuropaediatrics Department pays non établi dans la noticeÉtablissement de santé
-
Instituto de Salud Carlos III pays non établi dans la noticeOrganisme public
Department of Pediatric Neurology — University of Duisburg-Essen, Nationwide Children's Hospital et Great Ormond Street Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.