Duvyzat Approved by FDA As Treatment for Duchenne Muscular Dystrophy

Duvyzat (givinostat; Italfarmaco SpA, Milan, Italy), a histone deacetylase (HDAC) inhibitor, was approved by the Food and Drug Administration (FDA) to treat Duchenne muscular dystrophy (DMD) in individuals aged >6 years. This is the first nonsteroidal drug approved to treat DMD.

FDA approval was based upon results from the EPIDYS clinical trial (NCT02851797), a phase 3, randomized, double-blind, placebo-controlled trial, which evaluated the safety and efficacy of Duvyzat in ambulant boys with DMD. The study included 179 boys aged ≥6 years with genetically confirmed DMD, who were stratified based on their baseline vastus lateralis fat fraction (VLFF) into group A (VLFF >5% to ≤30%) and group B (VLFF ≤5% or >30%). Participants were randomized 2:1 to receive oral Duvyzat or placebo twice daily for 72 weeks, with dose adjustments based on weight and tolerability.

The study met the primary endpoint, which compared the mean change between baseline and 72 weeks in the ability to climb 4 stairs in the intention-to-treat, group A population. Additionally, secondary endpoints assessing muscle function and strength showed favorable results.

• Duvyzat-treated individuals showed a slower decline in performing the four-stair climb assessment compared to placebo-treated individuals (difference vs placebo of 1.78 seconds, P=.037).
• Duvyzat treatment was associated with 40% less decline in the North Star Ambulatory Assessment (NSAA) total score and item loss.
• Duvyzat-treated individuals had a 30% reduction in vastus lateralis fat fraction (VLFF), a predictor of loss of ambulation, compared to the placebo-treated cohort.

The most common adverse events associated with givinostat treatment were diarrhea (36% vs 18% with placebo) and vomiting (29% vs 13% with placebo). No treatment-related deaths occurred.

According to prescribing information provided for Duvyzat, health care providers need to evaluate patient’s platelet counts and triglycerides prior to prescribing Dyvyzat and on an ongoing basis following treatment. Duvyzat also may cause QTc prolongation, and patients taking medications associated with QTc prolongation or who have certain heart disease types should avoid taking Duvyzat.