Givinostat improved mobility, physical function in boys with Duchenne muscular dystrophy

Key takeaways:

• Givinostat met the primary study endpoint of improved time to climb four stairs.
• Consistent results were reported with secondary endpoints, including specific physical function items of NSAA.

Treatment with givinostat was associated with improvement in mobility and physical function compared with placebo in ambulant boys with Duchenne muscular dystrophy, according to a poster at the 2023 MDA Clinical & Scientific Conference.

“Givinostat is a novel orally active histone deacetylase inhibitor being developed for the treatment of [Duchenne muscular dystrophy],” Eugenio Mercuri, MD, PhD, professor of pediatric neurology and head of the pediatric neurology and psychiatry unit at Gemelli Hospital Catholic University Foundation in Rome, and colleagues wrote.

Seeking to determine safety and efficacy of givinostat in ambulant patients with Duchenne muscular dystrophy (DMD), Mercuri and colleagues conducted the 18-month Epidys study, a randomized, double-blind, placebo-controlled, multicenter phase 3 trial.

Researchers enrolled 179 boys, aged 6 years and older, and evaluated time to climb four standard stairs, as well as physical function (assessed by North Star Ambulatory Assessment [NSAA]), time to rise from floor, walking distance over 6 minutes, muscle strength measured by knee extension and elbow flexion, and fat fraction of vastus lateralis muscle.

Participants were randomized to receive givinostat or placebo oral suspension (10 mg/mL) twice daily.

According to results, patients on givinostat demonstrated a statistically significant difference from baseline to 18 months in time to climb four stairs (geometric least squares mean ratio = 0.86). Treatment with givinostat also was associated with less decline in NSAA total score (mean difference = 1.91 points), as well as 39% less cumulative item loss.

Further, analysis of 17 specific items related to physical function in the NSAA demonstrated a difference between treatment and placebo groups, especially in items most affected in patients of this age and stage of disease. Givinostat showed favorable tolerability, with reversible and manageable adverse effects related to thrombocytopenia and hypertriglyceridemia.

“The treatment effects on physical function assessed by the NSAA are considered clinically important and are related to how DMD boys function in clinically meaningful motor tasks,” Mercuri and colleagues wrote.