Eugenio Maria Mercuri
Safety and efficacy of delandistrogene moxeparvovec versus placebo in Duchenne muscular dystrophy (EMBARK): Pivotal Phase 3 Primary results
Autori
- JERRY R. MENDELL (CENTER FOR GENE THERAPY, NATIONWIDE CHILDREN’S HOSPITAL, COLUMBUS, OH, USA; THE OHIO STATE UNIVERSITY, COLUMBUS, OH, USA – At the time of study – NEUROPSICHIATRA INFANTILE)
- FRANCESCO MUNTONI (THE DUBOWITZ NEUROMUSCULAR CENTRE, NIHR GREAT ORMOND STREET HOSPITAL BIOMEDICAL RESEARCH CENTRE, GREAT ORMOND STREET INSTITUTE OF CHILD HEALTH UNIVERSITY COLLEGE LONDON, & GREAT ORMOND STREET HOSPITAL TRUST, LONDON, UK – NEUROPSICHIATRA INFANTILE)
- CRAIG M. MCDONALD (UC DAVIS HEALTH, SACRAMENTO, CA, USA – NEUROPSICHIATRA INFANTILE)
- EUGENIO MARIA MERCURI (PEDIATRIC NEUROLOGY INSTITUTE, CATHOLIC UNIVERSITY AND NEMO PEDIATRICO, FONDAZIONE POLICLINICO GEMELLI IRCCS, ROME, ITALY – NEUROPSICHIATRA INFANTILE)
- EMMA CIAFALONI (UNIVERSITY OF ROCHESTER MEDICAL CENTER, ROCHESTER, NY, USA – NEUROPSICHIATRA INFANTILE)
- HIROFUMI KOMAKI (TRANSLATIONAL MEDICAL CENTER, NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY, KODAIRA, TOKYO, JAPAN – NEUROPSICHIATRA INFANTILE)
- CARMEN LEON-ASTUDILLO (DEPARTMENT OF PEDIATRICS, UNIVERSITY OF FLORIDA, GAINESVILLE, FL, USA – NEUROPSICHIATRA INFANTILE)
- ANDRÉS NASCIMENTO (NEUROMUSCULAR UNIT, NEUROPAEDIATRICS DEPARTMENT, HOSPITAL SANT JOAN DE DÉU, FUNDACION SANT JOAN DE DÉU, CIBERER – ISC III, BARCELONA, SPAIN – NEUROPSICHIATRA INFANTILE)
- CRYSTAL PROUD (CHILDREN’S HOSPITAL OF THE KING’S DAUGHTERS, NORFOLK, VA, USA – NEUROPSICHIATRA INFANTILE)
- ULRIKE SCHARA-SCHMIDT (DEPARTMENT OF PEDIATRIC NEUROLOGY, CENTER FOR NEUROMUSCULAR DISORDERS IN CHILDREN AND ADOLESCENTS, UNIVERSITY CLINIC ESSEN, UNIVERSITY OF DUISBURG-ESSEN, ESSEN, GERMANY – NEUROPSICHIATRA INFANTILE)
- ARAVINDHAN VEERAPANDIYAN (ARKANSAS CHILDREN’S HOSPITAL, UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES, AR, USA – NEUROPSICHIATRA INFANTILE)
- CRAIG M. ZAIDMAN (DEPARTMENT OF NEUROLOGY, WUSTL, WASHINGTON, MO, USA – NEUROPSICHIATRA INFANTILE)
- MAITEA GURIDI (F. HOFFMANN-LA ROCHE LTD, BASEL, SWITZERLAND – CLINICAL SCIENTIST)
- ALEXANDER P. MURPHY (ROCHE PRODUCTS LTD, WELWYN GARDEN CITY, UK – CLINICAL SCIENTIST)
- CAROL REID (ROCHE PRODUCTS LTD, WELWYN GARDEN CITY, UK – STATISTICO)
- CHRISTOPH WANDEL (F. HOFFMANN-LA ROCHE LTD, BASEL, SWITZERLAND – SAFETY SCIENTIST)
- DAMON R. ASHER (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – MEDICAL AFFAIRS)
- EDDIE DARTON (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – FARMACOVIGILANZA)
- STEFANIE MASON (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – CLINICAL DEVELOPMENT)
- RACHAEL A. POTTER (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – CLINICAL DEVELOPMENT)
- TEJI SINGH (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – CLINICAL DEVELOPMENT)
- WENFEI ZHANG (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – BIOSTATISTICA)
- PAULO FONTOURA (F. HOFFMANN-LA ROCHE LTD, BASEL, SWITZERLAND – CLINICAL DEVELOPMENT)
- JACOB S. ELKINS (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – MEDICAL AFFAIRS)
- LOUISE R. RODINO-KLAPAC (SAREPTA THERAPEUTICS, INC., CAMBRIDGE, MA, USA – RICERCA E SVILUPPO)
- ON BEHALF OF THE EMBARK STUDY GROUP
Presentatore
EUGENIO MARIA MERCURI (PEDIATRIC NEUROLOGY INSTITUTE, CATHOLIC UNIVERSITY AND NEMO PEDIATRICO, FONDAZIONE POLICLINICO GEMELLI IRCCS, ROME, ITALY)
Modalità
Oral Communication
Abstract
Background and Objective:delandistrogene moxeparvovec is an adeno-associated viral vector-based gene transfer therapy, designed to compensate for absent functional dystrophin in Duchenne muscular dystrophy (DMD) by delivering a transgene encoding engineered micro-dystrophin. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221).
Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<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 pre-screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 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 group (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 safety profile observed to date.
Conclusions: Based on the totality of functional assessments, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.