A recent post hoc analysis of the phase 3 EPIDYS trial presented at MDA 2024 revealed significant positive outcomes with givinostat, a histone deacetylase inhibitor, among patients with Duchenne muscular dystrophy.
In a new supportive post hoc analysis from the phase 3 EPIDYS trial (NCT02851797), findings showed a positive significant difference with givinostat (Italfarmaco SpA), a proprietary histone deacetylase (HDAC) inhibitor, in motor function among patients with Duchenne muscular dystrophy (DMD) in comparison with controls. These results are consistent with efficacy in the prespecified analyses and emphasize the potential efficacy of givinostat in a broader context.1
In the overall intention-to-treat (ITT) population (n = 179), investigators reported that givinostat displayed a statistically significant difference compared with the control 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). Overall, investigators noted that the treatment effect estimates relating to the key secondary end points consistently favored givinostat over the control, which supports the primary end point result.
These findings were presented at the
READ MORE:
In the analysis, the investigators used the North Star Ambulatory Assessment (NSAA) to evaluate both the change from baseline at 18 months of the total score and the cumulative loss of NSAA items. In the findings, authors observed an association between givinostat treatment and a less decline in NSAA Total Score (mean difference, 1.50 points; nominal P = .035). Researchers noted that givinostat treatment in patients with DMD showed a good tolerability profile, lining with findings in prior studies in DMD and other diseases.
Givinostat is designed to inhibit HDACs, enzymes that prevent gene translation by changing the 3-dimensional folding of DNA in the cell. Weeks before an approval decision was expected for givinostat in late 2023, the
In the primary analysis, conducted on the target population (n = 120), findings showed a slower decline in givinostat-treated patients on the primary end point of climbing 4 stairs in comparison with placebo (difference, 1.78 seconds; P = .0345).3 In addition, fat infiltration in the vastus lateralis muscle of the thigh, considered a characteristic of disease progression in DMD, was assessed using a noninvasive objective imaging method called magnetic resonance spectroscopy. All told, givinostat treatment resulted in delayed fat infiltration by approximately 30% (difference vs placebo, –2.9%; nominal P = .035).
In terms of safety, 95% of the adverse events (AEs) observed in EPIDYS were mild to moderate in severity, with 3 (2.5%) boys withdrawing treatment because of an AE. Similar to previous studies, the AE occurred in at least 1 of 10 participants with diarrhea, abdominal pain, thrombocytopenia, hypertriglyceridemia, platelet decrease, and triglyceride increase. The therapy’s tolerability was managed with appropriate monitoring and dose adjustments, with no new safety concerns identified.
