For years, researchers have evaluated Italfarmaco’s givinostat for patients with Duchenne muscular dystrophy (DMD). In fact, a Phase 2/3 clinical trial showed that long-term givinostat treatment helped slow respiratory decline and loss of ambulation. As Muscular Dystrophy News describes, Italfarmaco then became curious about evaluating the treatment for patients with Becker muscular dystrophy (BMD), considering the similarities between the conditions. According to data from the ongoing Phase 2 clinical trial, researchers have shown that the drug, while not meeting all trial endpoints, does show some benefits for patients.

Givinostat

So what exactly is givinostat? According to Parent Project Muscular Dystrophy (PPMD), the investigational treatment is:

an ‘HDAC inhibitor’ in that it blocks enzymes called histone deacetylases (HDACs), which are involved in turning genes ‘on’ and ‘off’ within cells and can reduce muscle regeneration in Duchenne. By inhibiting HDAC activity givionostat may help to activate muscle repair mechanisms to increase muscle fiber regeneration, reduce inflammation, and reduce fibrosis [scarring].

Thus far, givinostat has received Rare Pediatric Disease, Orphan Drug, and Fast Track designations from the FDA.

Within this trial, 51 male patients with BMD enrolled. During the trial, researchers sought to understand the change in muscle fibrosis (primary endpoint), the changes in fat infiltration (secondary endpoint), and the changes in muscle atrophy (secondary endpoint). Findings showed:

• There was a histological difference between patients treated with givinostat and those treated with a placebo. Researchers surmise that this is one of the reasons why the trial failed to see a decline in muscle fibrosis.
• In patients taking givinostat, fat did not infiltrate muscle, which was a negative effect that those taking the placebo did experience. Additionally, patients taking givinostat saw almost no muscle atrophy. Within the group of those taking a placebo, one patient experienced a significant amount of muscle atrophy within the thigh.
• Givinostat does not benefit patients with BMD in terms of climbing stairs, time-to-rise, strength, or walking tests (as compared to the placebo). However, treated patients saw a slower decline in mobility.
• Side effects include thrombocytopenia (low/decreased platelet levels), diarrhea, and increased triglycerides.
• Ultimately, researchers determined that 50mg 2x daily was the ideal dose for patients with BMD.

Becker Muscular Dystrophy (BMD)

Becker muscular dystrophy (BMD) is one of nine forms of muscular dystrophy. Though similar to Duchenne muscular dystrophy (DMD), patients with BMD often see their condition progress more slowly and have a later onset. DMD gene mutations cause BMD. Ultimately, these gene mutations, inherited in an X-linked recessive pattern, prevent patients from producing enough dystrophin, a protein which strengthens and protects muscle fibers. Because of its inheritance pattern, a majority of patients with BMD are male. Due to the lack of functional dystrophin, patients with BMD experience progressive muscle weakness and loss of muscle mass in skeletal and cardiac muscles. In many patients, symptom onset occurs between ages 5-15. Symptoms include:

• Enlarged calf muscles
• Progressive muscle weakness beginning in the legs and pelvis
• Frequent tripping and falling
• Cardiomyopathy
• Fatigue
• Difficulty breathing or walking
• Scoliosis (abnormal spinal curvature)
• Exercise intolerance
• Loss of balance and coordination