O.13 Givinostat in DMD: results of the Epidys Study

Abstract

Givinostat is a novel orally active histone deacetylase (HDAC) inhibitor developed for the treatment of DMD. The Epidys Study is a randomized, double blind, placebo controlled, multicenter Phase 3 study to evaluate the efficacy and safety of givinostat in ambulant DMD patients. One-hundred and seventy-nine DMD boys aged ≥6 years at baseline were enrolled and 95% of them completed the study. The primary efficacy assessment was the time to climb 4 standard stairs (4SC). The primary endpoint was complemented by six key secondary efficacy endpoints: time to rise from floor, distance walked in 6 minutes using 6-Minute Walk Test, physical function assessed by North Star Ambulatory Assessment (NSAA), knee extension and elbow flexion muscle strength, and fat fraction of vastus lateralis muscle (VL MFF) evaluated by magnetic resonance spectroscopy. Treatment duration was 18 months. Epidys Study met the primary endpoint with a significant difference between treatment and placebo arm in change from baseline at 18 months in 4SC (GLSmean ratio [SD] = 0.86 [0.071]; p=0.0345). Overall, treatment effect estimates relating to the key secondary endpoints also consistently favoured givinostat over placebo supporting the primary endpoint result, with treatment effects on total NSAA, cumulative loss of function, and VL MFF reaching nominal statistical significance with p <0.05. Safety and tolerability profile was acceptable. In conclusion, Epidys Study met its primary endpoint with consistent results in the key secondary endpoints. Safety and tolerability profile in Epidys Study was consistent with previous studies of givinostat.