FDA Approves First Nonsteroidal Treatment for Patients With Duchenne Muscular Dystrophy

On March 21, the FDA approved givinostat, an oral histone deacetylase inhibitor, for the treatment of patients 6 years of age or older with Duchenne muscular dystrophy (DMD). It is the first nonsteroidal medication approved to treat patients with all genetic variants of DMD.

Duchenne muscular dystrophy is a rare neurological disorder that causes progressive muscle weakness due to a lack of muscle protein called dystrophin. It is the most common childhood form of muscular dystrophy and typically affects males. As their muscles deteriorate, patients with DMD have trouble walking as well as breathing issues, ultimately leading to early death.

Although the life expectancy for those with DMD has increased over the years (with some patients surviving beyond 30 years) the FDA’s approval of givinostat, which targets pathogenic processes to reduce inflammation and muscle loss, is a welcome treatment option for this patient population.

“DMD denies the opportunity for a healthy life to the children it affects," Emily Freilich, MD, Director of the Division of Neurology 1, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release. "The FDA is committed to advancing the development of new therapies for DMD. 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.”

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The approval was based on a randomized, double-blind, placebo-controlled 18-month phase 3 study. The primary endpoint was the change from baseline to month 18 using a four stair climb to measure muscle function. A secondary endpoint was the change in physical function during that same time period.

All participants received a standard of care steroid regimen throughout the study. Following 18 months of treatment, patients treated with givinostat showed statistically significant less decline in the time it took to climb four stairs compared with placebo. The mean change from baseline to month 18 in time to climb four stairs was 1.25 seconds for patients receiving givinostat compared with 3.03 seconds for patients receiving placebo.

Looking at physical function, researchers used the North Star Ambulatory Assessment (NSAA) scale, which measures the motor function in boys with DMD who are capable of walking. Results showed that patients treated with givinostat had less of a decline in their NSAA score after 18 months compared with the placebo group.

The most common adverse effects of givinostat were diarrhea, abdominal pain, a decrease in platelets—which can lead to increased bleeding—nausea/vomiting, an increase in triglycerides, and fever. The recommended dosage is determined by the individual’s body weight, and it should be administered orally twice daily with food.

Reference:
FDA Approves nonsteroidal treatment for Duchenne muscular dystrophy. News release. March 21, 2024. Accessed April 4, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-nonsteroidal-treatment-duchenne-muscular-dystrophy