The effects of Givinostat for Duchenne muscular dystrophy: a systematic review
TL;DR
Current evidence on the efficacy of Givinostat remains uncertain, while it may have little or no effect on the risk of any adverse events, and well-designed RCTs with larger sample sizes and varying disease stages are needed to reduce these uncertainties.
Abstract
Introduction: Givinostat, a histone deacetylase inhibitor, has been investigated for the treatment of Duchenne Muscular Dystrophy (DMD) and slow muscle degradation. DMD is a genetic neuromuscular degenerative disease that begins in early childhood. It is an X-linked recessive disorder characterized by mutations in the dystrophin gene and progressive and severe muscle weakness and atrophy are the main characteristics of this disease. DMD predominantly affects boys, while most females are asymptomatic carriers, with a global prevalence estimated at 19.8 cases per 100,000 live male births. Objective: To evaluate the efficacy and safety of Givinostat for individuals with DMD based on evidence from randomized controlled trials (RCTs). Methodology: We conducted a systematic review following PRISMA guidance, focusing on RCTs assessing Givinostat versus placebo, standard care, no treatment, or any active pharmacological intervention in DMD. CENTRAL, MEDLINE, Embase, PEDro and LILACS were searched (August 2025) without restrictions. Two reviewers independently selected studies, extracted data, and appraised risk of bias using the original Cochrane tool. Certainty of evidence was assessed using GRADE. The protocol was prospectively registered in the PROSPERO database (CRD420251107551). Results: Two RCTs were included, although one is still ongoing. EPIDYS (n=179) compared Givinostat (13 mg to 47 mg twice daily) with placebo for 72 weeks. There is uncertainty regarding the effects of Givinostat on global symptom assessment (mean difference [MD] 1.91; 95% CI 0.30 to 3.53; n=120; very low certainty), serious adverse events (risk ratio [RR] 2.07; 95% CI 0.45 to 9.44; n=179; very low certainty), functional capacity assessed by two different instruments (n=120; very low certainty), and quality of life (MD 3.70; 95% CI −2.30 to 9.70; n=120; very low certainty). Givinostat may have little or no effect on the risk of any adverse events (RR 1.02; 95% CI 0.94 to 1.10; n=179; low certainty). Conclusions: Current evidence on the efficacy of Givinostat remains uncertain, while it may have little or no effect on the risk of any adverse events. Further well-designed RCTs with larger sample sizes and varying disease stages are needed to reduce these uncertainties.