Givinostat's Multifactorial Mechanism of Action in Duchenne Muscular Dystrophy: Marcello Paglione, PhD

Givinostat (Duvyzat; Italfarmaco SpA), a proprietary histone deacetylase (HDAC) inhibitor, was recently FDA-approved as a treatment for patients with Duchenne muscular dystrophy (DMD), becoming the first nonsteroidal drug approved for all genetic variants of DMD.¹ The therapy, designed to inhibit HDACs, enzymes prevent gene translation by changing the 3-dimensional folding of DNA in the cell. The data from the phase 3 EPIDYS trial (NCT02851797) assessing givinostat in patients with DMD was the supporting basis of the approval.

EPIDYS, a randomized, double-blind, placebo-controlled, multicenter study, included 179 ambulant male individuals who were randomly assigned 2:1 to either oral givinostat or placebo for an 18-month treatment period. Of these, 120 boys formed the target population. In a new supportive post hoc analysis from EPIDYS, findings showed a positive significant difference with givinostat in motor function among patients with DMD in comparison with controls.² In the overall intention-to-treat (ITT) population (n = 179), investigators reported that givinostat displayed a statistically significant difference compared with controls in change from baseline at 18 months in the timed 4 stair climb (global longitudinal strain mean ratio, 0.84[SD, 0.069] P = .0116).

The findings from the post hoc analysis, presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 3-6, in Orlando, Florida, emphasize the efficacy of givinostat in a broader context. At the conference, Marcello Paglione, PhD, executive medical lead at Italfarmaco SpA, sat down with NeurologyLive^® to further discuss the role of HDAC in patients with DMD. He also talked about how givinostat's mechanism of action aims to mitigate the progression of the disease. In addition, Paglione spoke about ongoing research initiatives that are being pursued to further understand givinostat's efficacy and safety profile.