Background: Givinostat is an oral histone deacetylase inhibitor that was investigated in the phase 3, randomized, double-blind, placebo-controlled EPIDYS trial (NCT02851797). In the 2021 interim analysis of an ongoing, single-arm, open-label extension (OLE) study of the long-term safety, tolerability, and efficacy of givinostat (NCT03373968), givinostat-treated patients showed a delay in median age at persistent loss of ambulation (LoA; ie, permanent inability to walk independently) compared with a matched, natural history corticosteroid-treated external control group.
Objective: To evaluate the effect of longer-term givinostat treatment, in combination with standard-of-care corticosteroids, on LoA in patients with DMD aged ≥6 years using data through the 2023 cutoff, which provided a larger patient population and an additional 2 years of follow-up since the previous interim analysis.
Methods: The ongoing OLE study includes patients who completed a prior phase 2 givinostat study (NCT01761292) or EPIDYS (NCT02851797), as well as those who were screened but not randomized in EPIDYS. All patients who received ≥1 month of givinostat in combination with corticosteroids were included in the analyses. Median age at persistent LoA was calculated using Kaplan–Meier survival analysis in this population.
Results: Among the 225 patients analyzed, 78 experienced persistent LoA. The median (95% CI) age at persistent LoA was 17.3 (15.5-18.1) years.
Conclusions: This updated interim analysis evaluated LoA in patients with DMD with 2 additional years of data from the OLE. These updated OLE data suggest that givinostat consistently delays the onset of LoA in patients with DMD. Relative to published estimates from a meta-analysis reporting a median age at LoA of 11.0-13.4 years in patients treated with corticosteroids alone, the median age at persistent LoA with givinostat was 17.3 years, suggesting a delay in the loss of ambulation in patients treated with givinostat.