Givinostat improves range of motion, reduces decline of muscle function in DMD

Key takeaways:

• Treatment with givinostat reduced decline in time of four-stair climb by approximately 40% after 18 months.
• Givinostat demonstrated a favorable safety and tolerability profile.

Treatment with givinostat for ambulatory boys with Duchenne muscular dystrophy led to improved motion and reduced decline of muscle function and strength at 18 months, according to a poster at the 2024 MDA Clinical & Scientific Conference.

“There are currently limited FDA-approved treatment options for those diagnosed with Duchenne muscular dystrophy,” Matt Trudeau, head of ITF Therapeutics, the U.S. affiliate of manufacturer Italfarmco, told Healio in an email. “Our goal in researching givinostat and its potential to address the effects of [Duchenne muscular dystrophy] is to help slow progression of disease.”

Researchers sought to examine the rate of disease progression slowing of givinostat in a cohort of ambulatory boys with DMD, as well as to provide supplemental data through a post-hoc analysis using the study’s intent-to-treat (ITT) population.

The randomized, double-blind, placebo-controlled study was conducted in sites across the United States, Canada, Europe and Israel, evaluating safety and efficacy of givinostat in a cohort of ambulant pediatric DMD patients given corticosteroids for 6 or more months. In both the overall population (n = 179) and the target population (n = 120), participants were randomized 2:1 to receive either givinostat or placebo. A supportive post hoc analysis using an analysis of covariance (ANCOVA) was done to evaluate the impact of givinostat compared with the ITT population.

Primary endpoints included change in mean time of the four-stair climb (4SC) from baseline to 18 months, with secondary endpoints including mean change in North Star Ambulatory Assessment (NSAA), cumulative loss of function measured by NSAA, mean change in time to rise from floor, and overall muscle strength. NSAA was evaluated both as change from baseline at 18 months of the Total Score and as the cumulative loss of NSAA items. Safety was analyzed via treatment-emergent adverse events (TEAEs), serious adverse events and study discontinuation due to adverse events (AE), with the safety population defined as all participants who received at least 1 dose of givinostat.

According to results, those in the givinostat group showed a significantly slower 4SC decline compared with those given placebo in change from baseline (GLSmean ratio = 0.84 [0.069]). Overall, treatment effect estimates relating to the key secondary endpoints consistently favored givinostat over control supporting the primary endpoint result. Data were the same in the target population.

Researchers additionally found givinostat treatment was associated with less decline in NSAA Total Score (mean difference: 1.5 points), while also demonstrating a good tolerability profile.

A similar proportion of participants in each group experienced adverse events (95% vs. 93%), although the most common AEs of diarrhea and vomiting were recorded more than twice as many times in the givinostat cohort compared with placebo). A total of 3.4% in the treatment group recorded TEAEs that led to discontinuation.

“These data, which are highlighted in posters at the MDA conference this week, represent important progress towards givinostat's pending regulatory review and the opportunity to provide patients with access to another much-needed treatment option,” Trudeau told Healio.