The Epidys Givinostat Study in DMD: supportive results

Topic:

Clinical Trials

Poster Number: M163

Author(s):

Eugenio Maria Mercuri, MD, PhD, Paediatric Neurology and Centro Clinico Nemo, Claudia Brogna, MD, Centro Clinico Nemo, Catholic University, Rome, Italy, Craig Zaidman, MD, Washington University in St. Louis School of Medicine, Katherine Mathews, MD, FAAN, University of Iowa, Barry J Byrne, MD, PhD, University of Florida, Chamindra G. Laverty, MD, University of California, San Diego Department of Neuroscience, San Diego, CA, USA, SARA CAZZANIGA, Msc, ITALFARMACO S.P.A., Paolo Umberto Bettica, MD. PhD, Italfarmaco SpA, Craig McDonald, MD, UC Davis Health

Background: The Phase 3 Epidys study with givinostat in DMD met its primary endpoint with consistent results in the key secondary endpoints. The primary analysis was conducted in boys with baseline MRS vastus lateralis fat fraction >5–30% (Target Population, N=120). Here we present a supportive post-hoc analysis using the ITT population.
Methods: The Epidys Study was a randomized, double blind, placebo controlled, multicenter Phase 3 study to evaluate the efficacy and safety of givinostat in ambulant DMD patients. All patients were treated with steroids. In addition, patients were randomized to either givinostat or placebo (2:1). A supportive post-hoc analysis using an analysis of covariance (ANCOVA) was done to evaluate the impact of Givinostat versus control also on the overall ITT population (N=179). Both primary (i.e., the time to climb 4 standard stairs) and 6 key secondary endpoints were analyzed.
Results: In the overall ITT population, givinostat demonstrated a statistically significant difference versus control in change from baseline at 18 months in 4SC (GLSmean ratio [SD] = 0.84 [0.069]; p=0.0116). Overall, treatment effect estimates relating to the key secondary endpoints consistently favored givinostat over control 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: 1.50 points; nominal p=0.035). Givinostat treatment in DMD patients showed a good tolerability profile.
Conclusion: The Epidys Study successfully met its primary endpoint with consistent results in the key secondary endpoints. The post-hoc analysis of the overall ITT population were consistent with the prespecified analyses. Givinostat tolerability profile in study 48 was in line with results in previous studies in DMD and in other diseases.