EPIDYS Phase 3 Study: Givinostat Shows Promise in Treating DMD

A significant clinical trial for Duchenne muscular dystrophy (DMD) has reported positive findings, indicating a promising step forward in the treatment of this degenerative disease. The phase 3 EPIDYS study, conducted by Italfarmaco S.p.A., has shown that givinostat, an investigational drug, can potentially delay the progression of DMD when used in conjunction with corticosteroid therapy.

The EPIDYS trial, which is one of the largest phase 3 trials for DMD to date, involved 179 ambulant boys aged six and above. The study was designed as a multicentre, randomized, double-blind, placebo-controlled trial, with participants receiving either oral givinostat or a matching placebo alongside their corticosteroid treatment. The primary endpoint of the trial focused on the change in the four-stair climb assessment from baseline to 72 weeks, and the results demonstrated a meaningful treatment benefit with givinostat.

In addition to meeting its primary endpoint, the study also reported favorable outcomes on several key secondary endpoints. Notably, the North Star Ambulatory Assessment (NSAA), which measures motor function skills, indicated a 40% less decline in the givinostat group compared to the control group. Furthermore, magnetic resonance imaging showed a 30% reduction in the vastus lateralis fat fraction in those treated with givinostat, suggesting a delay in disease progression.

Givinostat was found to be well tolerated, with a safety profile that aligns with previous trials of the drug. The most common treatment-related adverse events were manageable with appropriate monitoring and dose adjustments, and no severe or serious adverse events were attributed to the treatment.

The positive results of the EPIDYS trial have led to the submission of a New Drug Application (NDA) to the U.S. FDA, with a PDUFA date set for March 21, 2024. Additionally, a Marketing Authorisation Application (MAA) has been submitted to the European Medicines Agency (EMA) and is currently under review.

Duchenne muscular dystrophy is a severe genetic disorder characterized by progressive muscle weakness and degeneration. It primarily affects boys and is caused by mutations in the dystrophin gene, leading to the absence of a functional dystrophin protein. This results in continuous muscle injury and chronic inflammation, which impairs muscle regeneration and leads to muscle replacement by fibrotic and fat tissue. The disease affects the ability to walk and can eventually impact heart and respiratory muscles, leading to premature death.

Givinostat, discovered through Italfarmaco Group's research in collaboration with Telethon and Duchenne Parent Project (Italy), is a histone deacetylase (HDAC) inhibitor. Its mechanism of action targets the deregulated activity of HDACs in dystrophic muscle, which is a consequence of the lack of dystrophin associated with DMD. By inhibiting this pathological overactivity, givinostat has the potential to address the cascade of events leading to muscle damage and slow down muscle deterioration.

Itafarmaco S.p.A., founded in 1938, is a global pharmaceutical company with a strong track record in the development and approval of pharmaceutical products. The company operates in over 60 countries and has demonstrated success in various therapeutic areas, including rare diseases such as DMD.

The publication of the EPIDYS trial results in The Lancet Neurology marks a significant milestone in the search for effective treatments for DMD. If approved, givinostat could offer a new therapeutic option for patients, regardless of the underlying gene mutation, providing hope for those affected by this devastating disease.