Givinostat for Becker muscular dystrophy: A randomized, placebo-controlled, double-blind study

Area of Science:

• Neurology
• Genetics
• Pharmacology

Background:

• Becker muscular dystrophy (BMD) is a genetic neuromuscular disorder with no approved treatments.
• Histone deacetylase (HDAC) inhibitors are being investigated for potential therapeutic benefits in genetic disorders.

Purpose of the Study:

• To evaluate the efficacy and safety of givinostat, an HDAC pan-inhibitor, in adult patients with Becker muscular dystrophy.
• To assess givinostat's impact on fibrosis, histological parameters, MRI/MRS measures, and functional outcomes in BMD.

Main Methods:

• A randomized, placebo-controlled trial involving 51 adult males with genetically confirmed BMD.
• Participants received either givinostat or placebo for 12 months, with a 2:1 randomization ratio.
• Primary endpoint: mean change in total fibrosis; secondary endpoints included histological, MRI, MRS, and functional assessments.

Main Results:

• The study did not meet its primary endpoint, showing no significant difference in total fibrosis between givinostat and placebo groups.
• MRI fat fraction analysis indicated a potential benefit, with givinostat showing a trend towards preventing increases observed in the placebo group.
• Givinostat was associated with a higher incidence of adverse events, mostly mild to moderate, compared to placebo.

Conclusions:

• Givinostat did not demonstrate efficacy in reducing fibrosis in Becker muscular dystrophy patients over 12 months.
• Preliminary MRI findings suggest givinostat might slow disease progression in BMD, warranting further investigation.
• The safety profile of givinostat in BMD patients requires careful consideration due to a higher rate of adverse events.