dc.contributor
Institut Català de la Salut
dc.contributor
[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
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
McDonald, Craig
dc.contributor.author
guglieri, michela
dc.contributor.author
Vučinić, Dragana
dc.contributor.author
Acsadi, Gyula
dc.contributor.author
Brandsema, John
dc.contributor.author
Bruno, Claudio
dc.contributor.author
Munell Casadesus, Francina
dc.date.accessioned
2025-12-20T16:17:14Z
dc.date.available
2025-12-20T16:17:14Z
dc.date.issued
2025-12-19T09:14:33Z
dc.date.issued
2025-12-19T09:14:33Z
dc.identifier
McDonald CM, Guglieri M, Vučinić D, Acsadi G, Brandsema JF, Bruno C, et al. Long-Term Evaluation of Givinostat in Duchenne Muscular Dystrophy, and Natural History Comparisons. Ann Clin Transl Neurol. 2025 Nov;12(11):2335–48.
dc.identifier
http://hdl.handle.net/11351/14162
dc.identifier
10.1002/acn3.70165
dc.identifier
001619574400023
dc.identifier.uri
http://hdl.handle.net/11351/14162
dc.description.abstract
Duchenne muscular dystrophy; Efficacy; Long term
dc.description.abstract
Distrofia muscular de Duchenne; Eficacia; Largo plazo
dc.description.abstract
Distròfia muscular de Duchenne; Eficàcia; Llarg termini
dc.description.abstract
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
dc.format
application/pdf
dc.relation
Annals of Clinical and Translational Neurology;12(11)
dc.relation
https://doi.org/10.1002/acn3.70165
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Distròfia muscular de Duchenne - Tractament
dc.subject
Inhibidors enzimàtics - Ús terapèutic
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Avaluació de resultats (Assistència sanitària)
dc.subject
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Histone Deacetylase Inhibitors
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Other subheadings::Other subheadings::/therapeutic use
dc.subject
DISEASES::Nervous System Diseases::Neuromuscular Diseases::Muscular Diseases::Muscular Disorders, Atrophic::Muscular Dystrophies::Muscular Dystrophy, Duchenne
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Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de histona desacetilasas
dc.subject
Otros calificadores::Otros calificadores::/uso terapéutico
dc.subject
ENFERMEDADES::enfermedades del sistema nervioso::enfermedades neuromusculares::enfermedades musculares::trastornos musculares atróficos::distrofias musculares::distrofia muscular de Duchenne
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Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
dc.title
Long-Term Evaluation of Givinostat in Duchenne Muscular Dystrophy, and Natural History Comparisons
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
