Givinostat is a novel orally active histone deacetylase (HDAC) inhibitor being 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 patients with DMD (Clinicaltrials.gov ID: NCT02851797). One-hundred and seventy-nine boys aged ≥6 years at baseline affected by DMD were enrolled and 95% of them completed the study. The primary efficacy assessment was the time to climb 4 standard stairs (4SC). Six key secondary efficacy endpoints 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 magnetic resonance spectroscopy. Treatment duration was 18 months.
The Epidys Study met its primary endpoint and givinostat demonstrated a statistically significant difference 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 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). Analysis of the effect on the 17 specific items of NSAA showed a difference between groups, in particular in the items which are mostly affected in patients of this age and disease stage. Givinostat treatment in patients with DMD showed a good tolerability profile in Study 48 with primary issues being reversible and manageable and related to thrombocytopenia, and hypertriglyceridemia.
In conclusion, the Epidys Study met its primary endpoint with consistent results in the key secondary endpoints. The treatment effects on physical function assessed by the NSAA are considered clinically important and are related to how DMD boys 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.