Vastus Lateralis Fat Fraction is Associated with Functional Efficacy Endpoints in Patients with Duchenne Muscular Dystrophy Treated with Givinostat in EPIDYS

Background and/or Objectives: Givinostat is an oral histone deacetylase inhibitor indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients aged ≥6 years, based on findings from the phase 3 EPIDYS study. Vastus lateralis fat fraction (VLFF) is inversely correlated with daily activity and muscle functionality and predicts loss of function in patients with DMD. In EPIDYS, treatment with givinostat delayed fat infiltration compared with placebo (least squares mean difference: -2.92%; p=0.035) after 18 months. The objective of this study was to determine whether VLFF is correlated with other measures of disease progression in patients from EPIDYS.

Design: Post hoc analysis.

Setting : 41 tertiary care sites in 11 countries.

Participants : Patients from EPIDYS with VLFF >5% and ≤30%.

Interventions: Givinostat (n=77) or placebo (n=37) in addition to standard of care (ie, corticosteroids).

Main Outcome Measures: The relationship between VLFF and key efficacy endpoints observed at the end of study (month 18), including the 4-stair climb (4SC), time to rise (TTR), 6-minute walking test (6MWT), and North Star Ambulatory Assessment (NSAA), was explored.

Results: VLFF had a relatively high reciprocal correlation with 4SC (0.539, p=0.026), 6MWT (−0.528, p=0.029), and NSAA (−0.527, p=0.030). The correlation between VLFF and TTR (0.409, p=0.100) was not statistically significant.

Conclusions: Based on these results, the observed VLFF in response to treatment with givinostat suggests an association with efficacy endpoints evaluated in EPIDYS. These findings are consistent with previous studies showing a strong relationship between VLFF and functional measures and suggest that reductions in VLFF are clinically meaningful in patients treated with givinostat.