TOPLINE:

Use of givinostat plus systemic corticosteroids for a mean of 560 days was associated with delays of 2-3 years in loss of key motor functions in patients with Duchenne muscular dystrophy (DMD), an open-label extension study showed. Additionally, most treatment-related adverse events (AEs) were considered to be mild or moderate.

METHODOLOGY:

• Nearly 200 boys aged 6 years or older with DMD and ambulation (94%) or without ambulation were included in the ongoing, multicenter, single-arm, open-label extension study evaluating long-term safety, tolerability, and efficacy of givinostat, a class I and II histone deacetylase inhibitor.
• All participants had completed one of two prior clinical studies (phase 2 and phase 3 EPIDYS trials). For the open-label extension, they continued receiving givinostat (n = 110), switched to givinostat from placebo (n = 54), or began taking givinostat (n = 30).
• The mean duration of givinostat exposure was 559.6 days within the extension study, with maximum exposure exceeding 8 years among participants included from prior studies.
• Patients received open-label givinostat oral suspension at a flexible, weight-based dose in addition to systemic corticosteroids, with follow-up visits occurring every 4 months.

TAKEAWAY:

• About 87% of patients reported at least one AE, with most considered to be mild or moderate in severity. The safety profile was consistent with previous studies, with no fatal or life-threatening events observed.
• The most common givinostat-related AEs were increased blood triglyceride levels, decreased platelet counts, and diarrhea. AEs leading to dose reduction were experienced by 15% of patients receiving givinostat throughout, 28% of those receiving prior placebo, and 13% of those not included in either group.
• Post hoc comparisons with two natural history datasets (Cooperative International Neuromuscular Research Group Duchenne Natural History Study and ImagingDMD) in propensity score-matched populations showed that the use of givinostat plus systemic corticosteroids was associated with a significant delay in loss of the ability to rise from the floor by a median of 2 years (hazard ratio [HR], 0.7; nominal P = .03), loss in the ability to complete the 4-stair climb test by a median of 3 years (HR, 0.4; nominal P < .001), and loss of ambulation by a median of 3 years (HR, 0.4; nominal P = .004).

IN PRACTICE:

“Overall, the safety and tolerability of long-term administration of givinostat in patients with DMD was consistent with previous studies. Comparisons with natural history data suggest that givinostat delays the occurrence of major disease progression milestones,” the investigators wrote.

SOURCE:

The study was led by Craig M. McDonald, MD, University of California Davis Health, Sacramento, California. It was published online on August 19 in the Annals of Clinical and Translational Neurology.

LIMITATIONS:

Results are limited to the participants who met inclusion or exclusion criteria and voluntarily continued in the long-term extension study. External control natural history databases were not contemporary with the current study. The number of observations beyond age 15 years was limited. Additionally, researchers could not control for corticosteroid regimen or changes in dose, regimens, or type of corticosteroid in long-term comparisons with natural history datasets.

DISCLOSURES:

This research was funded by Italfarmaco SpA and the National Institutes of Health. Several investigators reported having ties with various organizations and pharmaceutical companies, including the makers of the study drug. Full details are listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.