Sistema de Salut de Catalunya
Institut Català de la Salut
[McDonald CM] University of California Davis Health, Sacramento, California, USA. [Guglieri M] The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. [Vučinić D] Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia. [Acsadi G] Division of Neurology, Connecticut Children's, Hartford, Connecticut, USA. [Brandsema JF] Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. [Bruno C] Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genova, Italy. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health – DINOGMI, University of Genova, Genova, Italy. [Munell F] Secció de Neurologia Pediàtrica, Servei de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. European Reference Network for Neuromuscular Diseases (ERN-EURO-NMD), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-12-19T09:14:33Z
2025-12-19T09:14:33Z
2025-11
Duchenne muscular dystrophy; Efficacy; Long term
Distrofia muscular de Duchenne; Eficacia; Largo plazo
Distròfia muscular de Duchenne; Eficàcia; Llarg termini
Objectives This ongoing, open-label extension study is evaluating the long-term safety, tolerability, and efficacy of givinostat, a Class I and II histone deacetylase inhibitor, in patients with Duchenne muscular dystrophy (DMD). Methods The recruited patients completed one of two prior clinical studies (one Phase 2 and one Phase 3 [EPIDYS]), receiving givinostat or placebo, or were successfully screened but not randomized into EPIDYS. All receive givinostat oral suspension open-label at a flexible, weight-based dose in addition to systemic corticosteroids, and attend visits every 4 months. Results A total of 194 patients are included in the current analyses, with a mean duration of givinostat exposure (excluding use in prior studies) of 559.6 days (SD 373.0); when including use in the prior studies, the maximum exposure to givinostat was > 8 years. Although the majority of patients reported ≥ 1 adverse event (169/194 [87.1%]), most were mild/moderate in severity, and the safety profile of givinostat was consistent with prior studies. Post hoc comparisons with natural history datasets (ImagingDMD and CINRG) suggest, in propensity matched populations, givinostat added to systemic corticosteroids significantly delayed the loss of the ability to rise from the floor, the loss of the ability to complete the 4-stair climb test, and the loss of ambulation (by medians of 2.0–3.3 years; all nominal p < 0.05). Interpretation Overall, the safety and tolerability of long-term administration of givinostat in patients with DMD was consistent with previous studies. Comparisons with natural history data suggest that givinostat delays the occurrence of major disease progression milestones. Trial Registration EudraCT number: 2017-000397-10; ClinicalTrials.gov identifier: NCT03373968
Article
Published version
English
Distròfia muscular de Duchenne - Tractament; Inhibidors enzimàtics - Ús terapèutic; Avaluació de resultats (Assistència sanitària); CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Histone Deacetylase Inhibitors; Other subheadings::Other subheadings::/therapeutic use; DISEASES::Nervous System Diseases::Neuromuscular Diseases::Muscular Diseases::Muscular Disorders, Atrophic::Muscular Dystrophies::Muscular Dystrophy, Duchenne; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de histona desacetilasas; Otros calificadores::Otros calificadores::/uso terapéutico; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades neuromusculares::enfermedades musculares::trastornos musculares atróficos::distrofias musculares::distrofia muscular de Duchenne; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
Wiley
Annals of Clinical and Translational Neurology;12(11)
https://doi.org/10.1002/acn3.70165
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3396]
