Unleashing the Potential of Givinostat: A Novel Therapy for Duchenne Muscular Dystrophy

Purpose: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder with limited treatment options beyond corticosteroids, which have significant adverse effects. Givinostat, a histone deacetylase inhibitor, has recently emerged as a promising disease-modifying therapy. This commentary examines the therapeutic potential of givinostat, its mechanism of action, and the clinical evidence supporting its role in DMD treatment. Methods: A review of the EPIDYS Phase 3 trial and supporting clinical studies was conducted. The study included boys aged 6 to 17 years with genetically confirmed DMD, assessing givinostat's efficacy and safety over 18 months. Key endpoints included the North Star Ambulatory Assessment (NSAA), MRI-based muscle preservation, and adverse event (AE) profiles. Findings: Givinostat-treated patients demonstrated a 1.9-point higher NSAA score compared to placebo ( P = 0.03), with significant reductions in muscle fat infiltration (40% lower than placebo; P < 0.05). Functional tests showed trends toward improved stair-climbing ability, though not statistically significant. AEs included thrombocytopenia (20%) and hypertriglyceridemia (10%), necessitating monitoring but remaining manageable. Implications: Givinostat represents a paradigm shift in DMD management, offering benefits beyond corticosteroids by reducing fibrosis and promoting muscle regeneration. While its long-term safety and costeffectiveness require further evaluation, its combination potential with gene therapies highlights its importance in future DMD treatment strategies. Ongoing studies aim to refine its role in broader neuromuscular disorders. (c) 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )