FDA Approves Nonsteroidal DMD Drug

The U.S. Food and Drug Administration (FDA) announced that it’s approved Duvyzat (givinostat) oral medication for the treatment of Duchenne Muscular Dystrophy (DMD) in patients over the age of 6.

Duvyzat is the first nonsteroidal drug to earn approval to treat patients with every genetic DMD variation. Duvyzat’s a histone deacetylase (HDAC) inhibitor that works by singing out pathogenic processes to mitigate inflammation and muscle loss.

“The approval of Duvyzat (givinostat) provides another significant treatment option for people living with [DMD],” the Muscular Dystrophy Association’s Chief Research Officer, Sharon Hesterlee, PhD, said. “As more drugs are approved for DMD, we look forward to understanding if and how they might be used in combination.”

Young Men Suffer DMD Most

DMD, the most common childhood form of MD, targets boys almost exclusively. Life expectancy for DMD patients has grown recently, with some surviving 30 years past diagnosis.

According to the MDA, “(DMD) is a rare and progressive genetic muscle disease caused by the lack of a critical membrane-stabilizing protein called dystrophin, which results in muscle degeneration and weakness. DMD symptom onset is in early childhood, usually between ages 2 and 3.”

In Europe and North America, the prevalence of DMD is roughly 6 out of every 100,000 individuals. Doctors often diagnose the disease between ages 3 and 6 when children show early signs of significant muscle weakness, such as delayed ability to sit, stand, or walk and difficulties learning to speak. Over time, DMD becomes fatal as muscle degeneration disrupts lung and heart function.

Regulators evaluated Duvyzat’s efficacy with a randomized, double-blind, placebo-controlled 18-month phase 3 study. Every study participant continued to receive a standard-of-care steroid regimen throughout. And – after 18 months of treatment – Duvyzat patients exhibited 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 Duvyzat patients. Placebo pateients took 3.03 seconds.

“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,” the FDA’s Emily Freilich, M.D., explained in a press release. “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.”

Side Effects and Warnings

Duvyzat’s most common side effects include diarrhea, abdominal pain, a drop-off in platelets, nausea/vomiting, an uptick in triglycerides, and fevers.

Warnings suggest that healthcare providers should evaluate the patient’s platelet counts and triglycerides before prescribing Duvyzat. Regulators advise that patients with a low platelet count (less than 150 x 109/L) should avoid Duvyzat. The FDA adds that patients should have their platelet counts and triglycerides monitored during treatment. Medical professionals might need to adjust dosage in the case of moderate or severe diarrhea.

Finally, Duvyzat might also cause QTc prolongation, which can increase the risk of irregular heartbeats. Patients taking certain medications that also cause QTc prolongation or have certain types of heart disease should avoid taking Duvyzat.

The FDA granted this application priority review and fast-track designation. It also received orphan drug and rare pediatric disease designations.

Further Reading

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Perspectives on the New FDA Pregnancy and Lactation Labeling Rule