The US Food and Drug Administration (FDA) has approved givinostat (Duvyzat) for treatment of Duchenne muscular dystrophy (DMD) in patients aged 6 years or older.
Givinostat, a histone deacetylase inhibitor, is the first nonsteroidal drug approved to treat patients with all genetic variants of DMD. It works by targeting pathogenic processes to reduce inflammation and loss of muscle, the FDA explained in a news release announcing the drug's approval.
Givinostat is administered twice daily with food. The recommended dosage is based on body weight.
"DMD denies the opportunity for a healthy life to the children it affects. This approval provides another treatment option to help reduce the burden of this progressive, devastating disease for individuals impacted by DMD regardless of genetic mutation," Emily Freilich, MD, with the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, said in the release.
Approval was based on findings from the randomized, double-blind, placebo-controlled phase 3 EPIDYS trial. Givinostat, on a background of standard corticosteroid therapy, led to statistically and clinical meaningful benefits in ambulatory children with DMD compared with placebo, including reduced decline in muscle function and strength.
Although results in the four-stair climb assessment from baseline to 72 weeks, the trial's primary endpoint, worsened in both the treatment and placebo groups, the decline was significantly smaller with givinostat, as reported by Medscape Medical News.
Potential for Combination Therapy
"There is a tremendous unmet need for novel therapies in DMD that can achieve meaningful benefits for a broad range of patients," study investigator Craig M. McDonald, MD, with UC Davis Health, said in a company news release. "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."
The approval of givinostat "provides another significant treatment option" for people living with DMD," Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association (MDA), said in a separate statement.
Givinostat works differently than conventional DMD treatments, suggesting "the combination of this new drug with other therapies may further improve the lives of our patients living with DMD," added MDA's chief medical officer Barry Byrne, MD, PhD.
The most common side effects of givinostat are diarrhea, abdominal pain, a decrease in platelets potentially leading to increased bleeding, nausea/vomiting, an increase in triglycerides, and fever.
Prescribing information advises clinicians to evaluate a patient's platelet counts and triglycerides before prescribing givinostat. Patients with a platelet count < 50 × 109 cells/L should not take the drug. Platelet counts and triglyceride levels should be monitored as recommended during treatment to determine whether changes in dosage are needed. Dosage modifications may also be needed for moderate or severe diarrhea.
Givinostat may cause QTc prolongation, and patients taking certain medications that also cause QTc prolongation and those who have certain types of heart disease should avoid taking givinostat.
The FDA accepted the company's new drug application and granted priority review for givinostat in June 2023. Italfarmaco announced in November that the original Prescription Drug User Fee Act date, set for December 21, was extended to March 21 to allow the agency more time to review data submitted by the company.
Full prescribing information and a medication guide are available online.