Givinostat in DMD: Results of the EPIDYS Study with Particular Attention to NSAA

Résumé fourni par la source

Background: Givinostat is a novel orally active histone deacetylase (HDAC) inhibitor being developed for the treatment of DMD. Methods: EPIDYS study is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study to evaluate the efficacy and safety of Givinostat in ambulant patients with DMD. A total of 179 boys aged ≥6 years at baseline affected by DMD were enrolled and 95% of them completed the study. Primary efficacy assessment was the time to climb 4 standard stairs (4SC). Six key secondary efficacy endpoints were included: physical function assessed by North Star Ambulatory Assessment (NSAA), time to rise from floor, distance walked in 6 minutes using 6-minute walk test, knee extension and elbow flexion quantitative muscle strength, and fat fraction of vastus lateralis muscle (VL MFF) evaluated by MR spectroscopy. Treatment duration was 18 months. Results: EPIDYS study met its primary endpoint and Givinostat demonstrated a statistically significant difference in change from baseline at 18 months in 4SC (GLS mean ratio [SD] = 0.86 [0.071]; p = 0.0345). Overall, treatment effect estimates relating to the key secondary endpoints consistently favored Givinostat over placebo supporting the primary endpoint result. NSAA was evaluated both as change from baseline at 18 months of the total score and as the cumulative loss of NSAA items. Givinostat treatment was associated with less decline in NSAA total score (mean difference: 1.91 points; nominal p = 0.021) as well as 39% less cumulative item loss (nominal p = 0.02). Givinostat treatment showed a good tolerability profile with primary issues being reversible and related to thrombocytopenia, and hypertriglyceridemia. Conclusion: EPIDYS study met its primary endpoint with consistent results in the key secondary endpoints. The treatment effects on physical function are considered clinically important and are related to how boys with DMD function in clinically meaningful motor tasks. Givinostat tolerability profile in study 48 was in line with results in previous studies in DMD and in other diseases. Publication History Article published online: 13 November 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.