Givinostat efficacy in Duchenne muscular dystrophy: natural history comparison applying propensity score matching

Topic:

Clinical Trials

Poster Number: P87

Author(s):

David Gomez Andres, Hospital Universitario Vall De Hebron, Barcelona, Spain, Valeria Sansone, MD, Centro Clinico NEMO, University of Milan, Han Phan, MD, Rare Disease Research, Atlanta, Georgia, USA, Tracey Willis, MD, The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, UK, Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK, Mariacristina Scoto, MD PhD, UCL Great Ormond Street Institute of Child Health, London, UK, Krista Vandenborne, PhD, University of Florida, Sara Cazzaniga, Msc, Italfarmaco SpA., Nicoletta Coceani, MSc, Italfarmaco SpA, Paolo Bettica, MD, PhD, Italfarmaco SpA., Craig M McDonald, MD, University of California, Davis Health

The efficacy and safety of givinostat, an oral histone deacetylase inhibitor approved for the treatment of Duchenne muscular dystrophy (DMD) in patients aged ≥6 years, have been assessed in the phase 3 EPIDYS study in ambulant boys with DMD (NCT02851797). DSC/14/2357/51 (NCT03373968) is an ongoing open-label, long-term safety, tolerability, and efficacy study of givinostat in boys aged ≥6 years.

Using propensity score matching based on baseline functional test results and type of steroid, 142 patients from EPIDYS and DSC/14/2357/51 treated with givinostat were matched with 142 patients from ImagingDMD (NCT01484678) and CINRG (NCT00468832) DMD natural history studies (control group). Kaplan-Meier survival analyses were used to determine the median age at which DMD progression milestones, as measured by persistent loss to perform 4 stair climb [Lo4SC], loss of rise from floor [LoR], and loss of ambulation [LoA], occurred. Hazard ratios (HR) and 95% confidence intervals (CI) comparing the givinostat and control groups were calculated using Cox proportional hazards models.

Twenty-one (14.8%) patients exhibited Lo4SC in the givinostat group vs 52 (36.6%) in the control group (HR=0.39 [0.24, 0.65], p<0.001). The median (95% CI) age at Lo4SC was 17.9 (15.65, NE) years in the givinostat group vs 13.9 (13.50, 14.88) years in the control group. LoR occurred in 45 (31.7%) givinostat-treated patients compared to 61 (43.0%) controls (HR=0.66 [0.45, 0.96], p=0.028) at a median (95% CI) age of 14.9 (13.60, 15.97) vs 12.9 (12.20, 14.33) years, respectively. LoA occurred in 14 (9.9%) patients receiving givinostat compared to 39 (27.5%) in the control group (HR=0.42 (0.23, 0.76), p=0.004) at a median (95% CI) age of 18.1 (18.09, NE) vs 15.2 (14.70, 18.31) years, respectively. Compared with matched, steroid-treated controls, patients treated with givinostat experienced delayed disease progression. These results confirm the efficacy of givinostat, as demonstrated in the EPIDYS study, with longer-term treatment.