21/09/2025
GIVINOSTAT EFFECT ON RESPIRATORY FUNCTION IN DUCHENNE MUSCULAR DYSTROP HY BEFORE AND AFTER AMBULATION LOSS: RESULTS FROM EPIDYS, LONG-TERM SAFETY AND TOLERABILITY
EXTENSION, AND PRO-DMD-01 STUDIES
(AANEM 2025 Meeting)
Craig M. McDonald (Sacramento, CA), Chamindra G.
Laverty (San Diego, CA), Erika L. Finanger (Portland,
OR), James E. Signorovitch (Boston, MA), Andrea Parodi
(Milan, Italy), Federica Alessi (Milan, Italy), Sara
Cazzaniga (Milan, Italy), Paolo Bettica (Milan, Italy), Yann
INTRODUCTION: Givinostat, an oral histone deacetylase
inhibitor, is indicated for the treatment of Duchenne
muscular dystrophy (DMD) in patients aged over sixyears-
old.
OBJECTIVE: To evaluate the effect of givinostat on
pulmonary function in 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 over sixyears-
old) with DMD (NCT02851797) and its ongoing
open-label extension (NCT03373968) were indirectly
compared with PRO-DMD-01 (NCT01753804), a natural
history study of DMD disease progression. Matchingadjusted
indirect comparisons were used, adjusting for
patient characteristics at LoA. Forced vital capacity (FVC)
%percent predicted mean trajectories before and after
LoA were estimated using longitudinal mixed effects
models.
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,
two years before LoA, the weighted least squares mean
(SE) FVC %percent predicted was 91.3% (2.2%),
decreasing to 83.0% (2.3%) at LoA and 74.4% (2.4%) two
years post-LoA. The mean (SE) annual decline in FVC
percent 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 percent predicted was 5.6%
(2.1%) before LoA; this increased to 10.1% (2.2%) after
LoA.
SUMMARY/CONCLUSION: FVC% predicted trajectories
showed a slower and less pronounced decline in patients
treated with givinostat compared with those treated with
steroids only. These findings suggest improved pulmonary
function stabilization with givinostat treatment.
