Background: Givinostat, an oral histone deacetylase inhibitor, is approved in the US for the treatment of Duchenne muscular dystrophy (DMD) in patients aged ≥6 years.
Objectives: This study evaluated the effect of givinostat on the pulmonary function of patients who experienced loss of ambulation (LoA) during follow-up.
Methods: Data from the double-blind, randomized, phase 3 EPIDYS study in ambulant boys (aged ≥6 years) with DMD (NCT02851797) and its ongoing open-label extension (NCT03373968) were indirectly compared with results from PRO-DMD-01 (NCT01753804), a natural history study of disease progression among boys with genetically confirmed DMD. The comparison was balanced using the matching-adjusted indirect comparison method, adjusting for patient characteristics at LoA. Forced vital capacity (FVC) %-predicted mean trajectories before and after LoA were estimated using longitudinal mixed effects models to account for repeated measures and fitted to data over all available assessments during the pre- and post-LoA periods.
Results: This analysis included 56 patients treated with givinostat and steroids compared with published data on 51 patients from the PRO-DMD-01 study who received steroids only. Among weighted givinostat-treated patients, 2 years before LoA, the weighted least squares mean (standard error [SE]) FVC %-predicted was 91.3% (2.2%), decreasing to 83.0% (2.3%) at LoA and 74.4% (2.4%) 2 years post-LoA. The mean (SE) annual decline in FVC %-predicted was 3.6% (1.2%) before LoA and 3.9% (1.3%) after LoA. In the PRO-DMD-01 study, the mean (SE) annual decline in FVC %-predicted was 5.6% (2.1%) before LoA; this increased to 10.1% (2.2%) after LoA.
Conclusions: FVC% trajectories showed a slower and less pronounced decline in patients treated with givinostat in addition to steroids compared with those treated with steroids only, with no difference observed before and after LoA in the givinostat group. These findings suggest improved stabilization of pulmonary function with givinostat treatment.