FDA Approves Italfarmaco SpA’s Duvyzat for Duchenne Muscular Dystrophy

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The FDA has approved Italfarmaco SpA’s Duvyzat (givinostat) to treat patients 6 years of age and older with Duchenne muscular dystrophy (DMD).The FDA previously granted the histone deacetylase (HDAC) inhibitor with priority review, orphan drug designation, and rare pediatric disease designations.^1,2

“The FDA’s approval of Duvyzat for DMD, based on our robust and successful clinical development program, reflects Italfarmaco’s commitment to providing a safe and proven-effective therapy that can have a meaningful impact for people living with DMD,” Paolo Bettica, MD, PhD, chief medical officer, Italfarmaco Group, said in a press release. “We are grateful for the support of those living with DMD and their dedicated caregivers, which played a central role in helping us reach this landmark FDA approval. Our focus now is to make Duvyzat available as a treatment for DMD management in the US as quickly as possible.”¹

Duvyzat modifies deregulated activity of HDACs in the dystrophic muscle, which results from diminished dystrophin that occurs in patients with DMD. The drug’s mechanism of action has demonstrated the ability to limit HDAC pathological overactivity, which limits resulting muscle damage and deterioration, according to Italfarmaco.

“There is a tremendous unmet need for novel therapies in DMD that can achieve meaningful benefits for a broad range of patients. 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,” EPIDYS trial investigator Craig M. McDonald, MD, professor at the Department of Pediatrics and Physical Medicine Rehabilitation at the University of California Davis Health, said in a press release. “I would like to thank all patients and their families for participating in the clinical trials and for making this approval possible.”¹

The regulatory action was based on findings from the pivotal, multicenter, randomized, double-blind, placebo-controlled Phase III EPIDYS trial (NCT02851797). Investigators enrolled 179 ambulant males aged 6 years and older, who were randomly assigned at a 2:1 ratio to receive Duvyzat twice daily or placebo, as well as glucocorticosteroid treatment.³

The results demonstrated that patients administered Duvyzat experienced a statistically significant and clinically meaningful difference of a slower decline in the time to complete the four-stair climb assessment, which was the trial’s primary endpoint of climbing four stairs compared with placebo (difference, 1.78 seconds; P = .0345).³

The trial’s secondary endpoints included the North Star Ambulatory Assessment (NSAA) and time to rise test, both of which were consistent with the primary endpoint. Further, fat infiltration in the vastus lateralis muscle, which is associated with disease progression in DMD, was evaluated via magnetic resonance spectroscopy. Investigators found that Duvyzat led to delayed fat infiltration by approximately 30% (difference vs placebo, –2.9%; nominal P = .035).

“We are thrilled with the FDA’s approval of Duvyzat, a new therapy for DMD. It is an oral medication that will be available to every person 6 years and older with DMD. This brings great hope for the Duchenne community, and we believe this will be a key therapy to prevent disease progression in Duchenne,” Pat Furlong, founding president and CEO at Parent Project Muscular Dystropy, said in a press release.¹

References

1. Italfarmaco Receives FDA Approval for Duvyzat™ (givinostat) in Duchenne Muscular Dystrophy. Italfarmaco SpA. News release. March 21, 2024. Accessed March 22, 2024. https://www.businesswire.com/news/home/20240321735508/en/Italfarmaco-Receives-FDA-Approval-for-Duvyzat%E2%84%A2-givinostat-in-Duchenne-Muscular-Dystrophy

2. FDA Approves Nonsteroidal Treatment for Duchenne Muscular Dystrophy. FDA. News release. March 21, 2024. Accessed March 22, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-nonsteroidal-treatment-duchenne-muscular-dystrophy

3. Italfarmaco group announces positive topline data from phase 3 trial showing beneficial effect of givinostat in patients with Duchenne muscular dystrophy. News release. June 25, 2022. Accessed March 22, 2024. https://www.businesswire.com/news/home/20220625005001/en/Italfarmaco-Group-Announces-Positive-Topline-Data-from-Phase-3-Trial-Showing-Beneficial-Effect-of-Givinostat-in-Patients-with-Duchenne-Muscular-Dystrophy