The U.S. Food and Drug Administration (FDA) approved givinostat (branded as Duvyzat) on March 21, 2024, for treating Duchenne Muscular Dystrophy (DMD) in patients aged six years and older. This oral medication is the first nonsteroidal drug approved for all genetic variants of DMD, offering a new therapeutic option for those affected by this progressive disease.
Understanding Givinostat and Duchenne Muscular Dystrophy
Givinostat is a histone deacetylase (HDAC) inhibitor. HDACs are enzymes that compact DNA, reducing gene expression. By inhibiting HDACs, givinostat promotes a relaxed chromatin structure, increasing transcription of genes for muscle repair and anti-inflammatory responses. This helps reduce inflammation, promote muscle regeneration, and decrease muscle fibrosis and fat accumulation in DMD patients.
Duchenne Muscular Dystrophy is a rare, progressive genetic disorder primarily affecting males, with symptoms appearing between ages two and three. It is caused by mutations in the DMD gene, leading to a deficiency or absence of dystrophin, a protein essential for muscle cell integrity. Without dystrophin, muscle cells are damaged, resulting in progressive muscle degeneration and weakness. The disease initially impacts proximal muscles, such as those in the hips and thighs, and eventually affects muscles responsible for breathing and heart function.
The FDA Approval Process and Key Findings
Givinostat’s FDA approval followed a rigorous evaluation, including the pivotal Phase 3 EPIDYS clinical trial. This randomized, double-blind, placebo-controlled study enrolled 179 ambulant boys with DMD, aged six years and older. Participants received oral givinostat or a placebo twice daily, alongside standard corticosteroid treatment, for 18 months.
The EPIDYS trial met its primary endpoint, demonstrating a significant benefit in slowing disease progression. The primary outcome measured was the change from baseline to 72 weeks in the time it took participants to climb four stairs. Boys treated with givinostat showed a slower decline in this task compared to the placebo group.
Secondary endpoints supported these findings, including a 40% less decline in the North Star Ambulatory Assessment (NSAA) total score, which evaluates motor function. MRI assessments also showed a 30% reduction in fat infiltration in the vastus lateralis muscle, a predictor of disease progression. The FDA granted givinostat priority review, fast track, orphan drug, and rare pediatric disease designations, leading to accelerated approval.
What the Approval Means for Patients
Givinostat’s FDA approval provides a new treatment option for individuals with Duchenne Muscular Dystrophy aged six and older. This nonsteroidal medication offers an alternative approach to managing the disease, regardless of the specific genetic mutation. Its mechanism, targeting pathogenic processes to reduce inflammation and muscle loss, aims to slow disease progression.
This approval expands the therapeutic landscape for DMD. As an oral medication, givinostat may improve convenience for patients and caregivers. Adding givinostat to existing treatment strategies could enhance efforts to maintain motor function and improve quality of life for those with DMD.