At a watershed moment for Duchenne muscular dystrophy (DMD) treatment, privately held Italian drugmaker Italfarmaco has added a new therapeutic option to the armamentarium against the debilitating muscle-wasting disorder.
Late Thursday, the U.S. FDA gave a thumbs-up to Italfarmaco’s histone deacetylase (HDAC) inhibitor Duvyzat, also known as givinostat.
The approval makes the product the first nonsteroidal drug approved to treat patients with all genetic variants of DMD in the U.S., the FDA said in an approval announcement. Duvyzat, which is taken orally, is specifically cleared to treat DMD in patients ages 6 and older, Italfarmaco said in a separate release.
DMD, which is the most common form of muscular dystrophy around the world, is a severe neuromuscular genetic disease marked by progressive muscle weakness and degeneration. The disease is caused by mutations in the dystrophin gene that lead to an absence of functional dystrophin proteins, in turn leaving muscle fibers prone to injury, inflammation and impaired regeneration and replacement. DMD primarily affects boys, but girls can be carriers of the disease, according to the Muscular Dystrophy Association.
Boasting a unique mechanism of action, Duvyzat works by modulating the deregulated activity of HDACs in the dystrophic muscle, which Italfarmaco says is a major consequence of the dystrophin deficit associated with DMD. By inhibiting HDAC overactivity, Duvyzat is designed to address the cascade of events leading to muscle damage, ultimately slowing down muscle deterioration, Italfarmaco said.
Citing the “tremendous unmet need” for DMD therapies that can help a broad range of patients, Craig McDonald, M.D., an investigator on Duvyzat’s pivotal phase 3 trial, said in a statement that Italfarmaco’s drug has the potential to become a “key component of the standard of care for people living with DMD.”
The FDA based its approval on results from Italfarmaco’s phase 3 EPIDYS trial, which looked at 179 boys ages 6 and up who received either Duvyzat twice daily or placebo in addition to glucocorticosteroid treatment. At the trial’s 18-month mark, patients on Duvyzat showed significantly less decline in the time it took to complete a four-stair climb measure of muscle function.
With an approval in hand, Italfarmaco’s next goal is to get Duvyzat to U.S. patients “as quickly as possible,” according to the company’s chief medical officer Paolo Bettica, M.D., Ph.D.
To that end, the company has “significantly expanded its U.S. presence” with the launch of subsidiary ITF Therapeutics, which will handle marketing for the drug in the States. Italfarmaco said Thursday that ITF is working closely with healthcare providers, patient advocacy groups and payers to help get Duvyzat on pharmacy shelves.
Privately held Italfarmaco was established in 1938 and currently operates in Italy and abroad from its headquarters in Milan. The company mainly makes drugs for cardiovascular, immuno-oncologic and gynecological disorders, according to its website.
With its Duvyzat green light, Italfarmaco will now have to go up against the likes of Sarepta Therapeutics, which boasts a suite of exon-skipping therapies for DMD such as Exondys 51, Vyondys and Amondys.
Meanwhile, Sarepta made a splash last summer with the FDA approval of its DMD gene therapy Elevidys, which has become one of the world’s most expensive drugs with a price tag of $3.2 million.
Elevidys works by delivering a micro-dystrophin-encoding gene into a patient’s muscle tissue to prompt production of the micro-dystrophin protein.
As Sarepta waits on a potential label expansion for Elevidys, the company said in late February that it’s seen early success with the gene therapy’s launch. The drug brought home total sales of $200.4 million last year, with $131.3 million coming in 2023’s fourth quarter.
Elsewhere, Santhera Pharmaceuticals and Catalyst Pharmaceuticals in October received an FDA nod for their own DMD therapy—a dissociative steroid known as Agamree, or vamorolone.
And, just this week, PTC Therapeutics revealed plans to resubmit its application for the nonsense mutation DMD candidate Translarna to the FDA by the middle of the year. The move comes after the U.S. regulator snubbed PTC’s drug in 2016 and 2017.