FDA gives priority review to oral givinostat in treating DMD

Decision on therapy, aiming to promote muscle repair, likely in December

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by Andrea Lobo |

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The U.S. Food and Drug Administration (FDA) has accepted and given priority review to Italfarmaco Group’s application requesting that oral givinostat be approved to treat Duchenne muscular dystrophy (DMD).

Priority review, which shortens the consideration period to six months from 10, is given to therapies with the potential to markedly improve care for serious conditions. An FDA decision is expected on or before Dec. 21.

“The FDA’s communication on our [application] and the priority review for givinostat represents a major milestone … and is a significant step forward in the search for effective treatments against this debilitating rare disease,” Paolo Bettica, MD, PhD, chief medical officer at Italfarmaco, said in a company press release.

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Givinostat works to promote activity in genes needed for muscle regeneration

Givinostat works to inhibit the activity of histone deacetylases (HDACs), enzymes that change how DNA folds in cells and block the activity of certain genes, including those needed for muscle regeneration. HDACs are known to be overactive in DMD patients, contributing to muscle degeneration.

By blocking these enzymes, the treatment is expected to promote muscle repair, reduce inflammation, and lessen muscle scarring (fibrosis) and fat accumulation.

The FDA submission was largely supported by data from the EPYDYS Phase 3 trial (NCT02851797), which enrolled 179 boys with DMD, ages 6-17, who were able to walk.

Patients, all on stable corticosteroid use for at least six months, were randomly assigned to an oral suspension containing givinostat or a placebo, taken twice daily for 18 months. They continued to use steroids during the trial.

The trial’s main goal was to determine changes with treatment in the time needed to climb four stairs. Secondary measures included changes in other measures of motor function, muscle strength, and fat accumulation in muscles. Safety also was assessed.

Phase 3 EPYDYS trial showed slower motor function decline in treated boys

Results showed the treatment significantly slowed motor function decline, with patients on a placebo requiring 1.78 more seconds to climb four stairs than those on givinostat after 18 months, the company reported.

Other functional tasks, such as the time to rise from the floor, walking assessments, and muscle strength, all were consistent with primary trial findings. Givinostat’s use also delayed fat infiltration in thigh muscle, characteristic of disease progression, by about 30%.

The most common adverse events observed in boys taking givinostat included diarrhea, abdominal pain, low platelet levels, and high levels of triglycerides, a type of fat. Most of side effects were deemed mild to moderate in severity, with three boys (2.5%) discontinuing treatment due to a side effect.

“In our Phase 3 trial, givinostat demonstrated that it can slow DMD progression, thereby potentially giving young boys and their families a treatment option to retain motor function,” Bettica said.

Givinostat has been given rare pediatric disease, orphan drug, and fast track designations by the FDA, all meant to support the development of medicines targeting unmet needs.

The European Medicines Agency (EMA) also designated givinostat an orphan drug for DMD, and the company is moving to file a similar approval application with EU regulators.

Givinostat also has been tested in adults with Becker muscular dystrophy. Top-line results from a Phase 2 trial (NCT03238235) showed that treatment failed to reduce muscle scarring, a main trial goal, but its use stopped further muscle shrinkage and fat infiltration, suggesting it may slow or prevent disease progression.