FDA Approves Italfarmaco’s Duvyzat for DMD

Rare Daily Staff

The U.S. Food and Drug Administration approved Italfarmaco S.p.A.’s Duvyzat for the treatment of patients 6 years or older with the rare, neuromuscular condition Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular genetic disease characterized by progressive muscle weakness and degeneration and is the most common type of muscular dystrophy globally. DMD is caused by mutations in the dystrophin gene that result in the absence of a functional dystrophin protein. Without dystrophin, muscle fibers are highly susceptible to injury and this continuous muscle injury leads to chronic inflammation, impairment of muscle regeneration, and muscle replacement by fibrotic and fat tissue. The disease primarily affects boys, with symptoms usually first seen between two and five years of age. Symptoms worsen over time affecting the ability to walk. Eventually, heart and respiratory muscles are affected, which are the two main causes of premature death.

Duvyzat is the product of a collaboration between Italfarmaco, Telethon, and Duchenne Parent Project in Italy. Duvyzat is a histone deacetylase (HDAC) inhibitor that modulates the deregulated activity of HDACs in the dystrophic muscle, which is a major consequence of the lack of dystrophin associated with DMD. Duvyzat’s mechanism of action has the potential to inhibit HDAC pathological overactivity in an effort to address the cascade of events leading to muscle damage, thereby counteracting the disease pathology, and slowing down muscle deterioration.

Duvyzat received priority review, orphan drug, and rare pediatric disease designations from the FDA. The company submitted a Marketing Authorization Application for the drug as a potential treatment for DMD to the European Medicine Agency that is currently under review. Italfarmaco is also working with other regulatory agencies.

The approval is based on the results of the pivotal multicenter, randomized, double-blind, placebo-controlled phase 3 EPIDYS trial. In the EPIDYS study, a total of 179 ambulant boys 6 years of age or older received either Duvyzat twice daily or placebo, in addition to glucocorticosteroid treatment.

The EPIDYS study met its primary endpoint demonstrating that patients on Duvyzat showed a statistically significant and clinically meaningful difference in time to complete the four-stair climb assessment. Duvyzat also showed favorable results on key secondary endpoints including North Star Ambulatory Assessment, and fat infiltration evaluation by magnetic resonance imaging.

The majority of adverse effects observed with Duvyzat were mild to moderate in severity. Results from this study were published in The Lancet Neurology in March 2024.

“There is a tremendous unmet need for novel therapies in DMD that can achieve meaningful benefits for a broad range of patients,” said Craig McDonald, professor at the Department of Pediatrics and Physical Medicine Rehabilitation at the University of California Davis Health and investigator for the EPIDYS trial. “Duvyzat’s unique mechanism of action has shown a positive risk/benefit profile and the ability to delay disease progression, supporting its potential to become a key component of the standard of care for people living with DMD.”

Italfarmaco has created a new, fully owned subsidiary, ITF Therapeutics that will be responsible for commercializing ITF Therapeutics in the United States.

Photo: Craig McDonald, professor at the Department of Pediatrics and Physical Medicine Rehabilitation at the University of California Davis Health and investigator for the EPIDYS trial