EMA starts review of Italfarmaco's Duchenne drug

Italfarmaco's marketing application for HDAC inhibitor givinostat as a treatment for Duchenne muscular dystrophy (DMD) has been accepted by the EMA, setting up an approval decision in 2024.

The Milan-based drugmaker filed for approval of the drug in the US earlier this year, with a priority review that should see a decision coming from the FDA by 21st December.

Givinostat is thought to restore muscle regeneration, increase muscle mass, and reduce inflammation and scar tissue accumulation in boys with DMD, and has been tested in the placebo-controlled phase 3 EPIDYS study involving 179 boys with DMD aged six and over who were able to walk (ambulatory).

The trial showed slower disease progression over 18 months of treatment with givinostat, including a slower decline from baseline in the time needed to climb four stairs compared to placebo, with mostly minor to moderate side effects. The drug and control were given on top of standard corticosteroid therapy for the patients, who had an average age of nine years.

Secondary results from the study included a slower decline in North Star Ambulatory Assessment (NSAA), time to rise and muscle strength analyses compared to placebo, as well as a reduction in the tendency for fat to accumulate within thigh muscles – a biomarker for worsening DMD symptoms.

The results followed a phase 2 trial that showed an increase in muscle fibre regeneration, as well as a reduction in tissue damage and inflammation in children given givinostat on top of steroid therapy.

Italfarmaco's chief medical officer, Paolo Bettica, said approval of givinostat could benefit DMD patients for whom no effective treatments are currently available, by preserving their motor skills and muscle strength.

"Now that our market authorisation application is under review, we are looking forward to working with the regulatory authorities to bring this treatment option to patients affected by this devastating disease, with the goal of providing therapeutic benefit and increasing their quality of life," he added.

The mechanism behind its action remains unclear and appears to be unrelated to the mutation in the dystrophin gene that lies at the heart of DMD.

Italfarmaco's drug could provide a way to preserve muscle function across a broad spectrum of patients, including those who may not be eligible for gene therapies that are starting to emerge for DMD and tend to be used in younger patients.

In June, the FDA approved Sarepta's Elevidys (delandistrogene moxeparvovec) as the first gene therapy for DMD, limited for use in ambulatory patients aged four to five.