Efficacy of Givinostat in the Off-Target Population of EPIDYS: A Subgroup Analysis

Topic:

Clinical Trials

Poster Number: P77

Author(s):

Richard S Finkel, MD, St. Jude Children’s Research Hospital, Han Phan, MD, Rare Disease Research, Atlanta, Georgia, USA, Federica Alessi, Italfarmaco SpA., Sara Cazzaniga, Msc, Italfarmaco SpA., Paolo Bettica, MD, PhD, Italfarmaco SpA., Chamindra Laverty, MD, University of California

Background: Givinostat, an oral histone deacetylase inhibitor, recently received US Federal Drug Administration approval for the treatment of boys aged ≥6 years with Duchenne muscular dystrophy (DMD). The efficacy and safety of givinostat were evaluated in the double-blind, randomized, phase 3 EPIDYS study in ambulant boys (aged ≥6 years) with DMD having baseline vastus lateralis fat fraction (VLFF) >5% but ≤30% (primary analysis/target population) (NCT02851797).

Objectives: The objective of this analysis was to evaluate givinostat efficacy, as measured by the change in a 4-stair climb (4SC) time (seconds) from baseline to month 18, in a subgroup of patients who did not meet the VLFF criterion (off-target population), defined by VLFF ≤5% or >30%.

Results: Of 179 patients enrolled in EPIDYS, 59 were in the off-target group (37 givinostat/22 placebo), and 120 were in the target group (81 givinostat/39 placebo). The givinostat dose was weight-based and flexible; all patients received chronic corticosteroids. The baseline 4SC mean (SD) time was 3.9 (1.4) and 3.7 (1.6) s in the off-target givinostat and placebo groups, respectively, and 3.4 (1.1) and 3.5 (1.3) s in the target groups. The nominally higher baseline 4SC time in the off-target groups suggests a more advanced disease. At month 18, the 4SC mean (SD) time was 6.6 (7.9) and 9.8 (13.3) s in the off-target givinostat and placebo groups, respectively, and 4.7 (3.2) and 6.4 (7.7) s in the target groups. Although the off-target subgroup was not powered to detect a statistically significant difference, the least-squares mean difference relative to placebo indicated a 2.78 s smaller decline with givinostat. In the target group, a 1.78 s smaller decline was observed for givinostat relative to placebo (p=0.037).

Conclusions: These findings suggest that givinostat efficacy is consistent in a relatively more advanced disease population. All patients with DMD, including those not meeting the target population criteria, could have the potential for treatment benefits with givinostat.