FDA Approves Nonsteroidal Treatment for Duchenne Muscular Dystrophy

2024-03-21

临床3期临床结果上市批准快速通道孤儿药

SILVER SPRING, Md., March 21, 2024 /PRNewswire/ -- Today, the U.S. Food and Drug Administration approved Duvyzat (givinostat) oral medication for the treatment of Duchenne Muscular Dystrophy (DMD) in patients six years of age and older. Duvyzat is the first nonsteroidal drug approved to treat patients with all genetic variants of DMD. It is a histone deacetylase (HDAC) inhibitor that works by targeting pathogenic processes to reduce inflammation and loss of muscle. "DMD denies the opportunity for a healthy life to the children it affects. The FDA is committed to advancing the development of new therapies for DMD," said Emily Freilich, M.D., director of the Division of Neurology 1, Office of Neuroscience in the FDA's Center for Drug Evaluation and Research. "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." DMD is the most common childhood form of muscular dystrophy and typically affects males. It is a rare neurological disorder which causes progressive muscle weakness due to a lack of muscle protein called dystrophin. Over time, the muscles deteriorate causing problems with walking and muscle strength and ultimately problems with breathing leading to early death. Life expectancy for those with DMD has increased over the years, with some patients surviving beyond 30 years. Duvyzat's efficacy for the treatment of DMD was evaluated in 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. All participants continued to receive a standard of care steroid regimen throughout the study and, after 18 months of treatment, patients treated with Duvyzat showed statistically significant less decline in the time it took to climb four stairs compared to placebo. The mean change from baseline to Month 18 in time to climb four stairs was 1.25 seconds for patients receiving Duvyzat compared to 3.03 seconds for patients receiving placebo. A secondary efficacy endpoint was the change from baseline to month 18 in physical function as assessed by the North Star Ambulatory Assessment (NSAA)—a scale commonly used to rate the motor function in boys with DMD who are capable of walking. Compared to placebo, patients treated with Duvyzat saw less worsening in their NSAA score after 18 months. The most common side effects of Duvyzat are diarrhea, abdominal pain, a decrease in platelets—which can lead to increased bleeding—nausea/vomiting, an increase in triglycerides (a type of fat in the body) and fever. The prescribing information for Duvyzat includes warnings which state that health care providers should evaluate the patient's platelet counts and triglycerides before prescribing Duvyzat. Patients with a platelet count less than 150 x 109/L should not take Duvyzat. Platelet counts and triglycerides should be monitored as recommended during treatment to determine if changes in dosage are needed. Dosage modifications may also be needed for moderate or severe diarrhea. Duvyzat may also cause QTc prolongation, which can increase the risk for irregular heartbeats. Patients taking certain medications that also cause QTc prolongation or have certain types of heart disease should avoid taking Duvyzat. The recommended dosage of Duvyzat is determined by the individual's body weight. It should be administered orally twice daily with food. The FDA granted this application priority review and fast track designation. It also received orphan drug and rare pediatric disease designations. The approval of Duvyzat was granted to Italfarmaco S.p.A. Additional Resources: Duchenne muscular dystrophy - About the Disease - Genetic and Rare Diseases Information Center The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.