Background/Purpose: Givinostat, an oral histone deacetylase inhibitor, has been investigated for Duchenne
muscular dystrophy (DMD) treatment in patients aged ≥6 years. Safety data from the
ongoing long-term study of givinostat were evaluated (NCT03373968).
Methods: This is an ongoing open-label, long-term safety, tolerability, and efficacy study
of givinostat in boys who completed or were screened but not randomized in previous
DMD givinostat studies.
Results: As of December 31, 2021, data cutoff, 194 patients have enrolled: givinostat (n = 110), prior placebo (n = 54), and not included in prior study (n = 30). All patients received givinostat and corticosteroids. Safety data were evaluated
for patients who received ≥1 givinostat administration. The mean duration of givinostat
exposure was 616, 506, and 451 days in the givinostat, prior placebo, and not-included
groups, respectively. Overall, 87.1% of patients reported ≥1 treatment-emergent adverse
event (TEAE), with similar incidence among all groups. Most TEAEs were mild to moderate
in severity. Among the most frequently reported TEAEs (≥10% of the overall population),
diarrhea was reported more frequently by the prior placebo (27.8%) and not-included
(36.7%) groups compared with the givinostat group (18.2%). More falls were reported
by the givinostat group (20.0%) compared with the prior placebo (9.3%) and not-included
(13.3%) groups. More reports of thrombocytopenia were observed in the prior placebo
group (20.4%) compared with the givinostat (9.1%) and not-included (10.0%) groups.
The givinostat group reported pyrexia (17.3%), increased blood triglycerides (12.7%),
and decreased platelet count (9.1%); the incidence of these TEAEs in the prior placebo
group was 13.0, 16.7, and 14.8%, respectively, and 6.7% for each TEAE in the not-included
group. Decreased platelets and increased triglycerides followed by stabilization are
consistent with givinostat treatment initiation.
Conclusion: These results are consistent with the known safety profile of givinostat.
