Long-Term Data Reinforce Givinostat Efficacy, Safety in DMD

Givinostat (Duvyzat; ITF Therapeutics) in combination with corticosteroids delayed Duchenne muscular dystrophy (DMD) progression and demonstrated long-term safety and tolerability in ambulatory patients aged 6 and older, according to a study published in Annals of Clinical and Translational Neurology.1

The findings, which come from open-label extensions of phase 2 and phase 3 (EPIDYS; NCT03373968) trials of givinostat in DMD, suggest the class I and II histone deacetylase inhibitor benefits patients across treatment groups and has positive impacts on key mobility aspects, including rising from the floor, climbing stairs, and ambulation.

"These data represent an important step in building a robust body of evidence for the long-term use of givinostat in DMD," Paolo Bettica, MD, PhD, chief medical officer at Italfarmaco, said in a statement.2 "The sustained benefit observed across functional outcomes reinforces the potential of givinostat to meaningfully alter the course of the disease. With its well-established safety profile and ease of administration, givinostat continues to emerge as a valuable treatment option for patients affected by DMD and their families."

Givinostat showed long-term benefits across treatment groups and in multiple mobility aspects in patients with DMD. | Image credit: MQ-Illustrations - stock.adobe.com

After propensity matching, the analysis included 142 patients who received givinostat and a natural history cohort of 142 patients. The mean duration of exposure to givinostat in the study was 559.6 days, and maximum exposure was more than 8 years when including use in prior studies.

Patients in the givinostat cohort showed delayed disease progression vs the matched natural history cohort across study end points. The loss of ability to rise from the floor was delayed by a median of 2 years with givinostat vs natural history (HR, 0.66; 95% CI, 0.45-0.96; nominal p = .028). The loss of 4-stair climb ability was delayed by 3.3 years (HR, 0.39; 95% CI, 0.24-0.65; nominal p < .001), and loss of ambulation was delayed by 2.9 years (HR, 0.42; 95% CI, 0.2-0.76; nominal p = .004). In an analysis including the overall population from the givinostat study compared with 2 natural history datasets, the findings were similar.

The authors noted that in the natural history cohort, patients were less likely to be receiving deflazacort (Emflaza; PTC Therapeutics) vs the givinostat cohort. Propensity matching improved this variation, but a further analysis including only individuals in the propensity-matched cohort receiving deflazacort found similar results. The most common adverse events that were considered related to treatment were increased blood triglyceride levels, decreased platelet counts, and diarrhea, which are known AEs associated with givinostat.

"These new findings show that treatment with givinostat continues to have a positive impact by addressing symptoms that patients are most concerned about and that these long-term benefits are achieved over several years while treatment remains safe and tolerable," study author Craig M. McDonald, MD, chair of the Department of Physical Medicine & Rehabilitation and professor in the departments of Pediatrics and Physical Medicine & Rehabilitation at the University of California Davis Health, said in a statement.2

The authors noted several study limitations, including that the results are limited to the population who met inclusion and exclusion criteria and took part in the long-term extension study. Despite propensity matching, the comparison was also indirect between givinostat-treated patients and the natural history control cohort. There was also no way of controlling for corticosteroid regimens. The authors also noted that all end points in the long-term extension study were not explored in the 2 natural history data sets, which limited the end points that could be used in the comparisons. However, those compared reflect main milestones in DMD progression, they explained.

“Overall, the safety and tolerability profile of long-term administration of givinostat in patients with DMD was consistent with the results of previous, shorter duration studies,” the authors concluded. “In addition, the efficacy benefit in terms of functional evaluations seen in these prior studies is consistent with the long-term data from this study, including the natural history comparisons. Patients continue ongoing follow-up in this open-label extension study.”

References

1. McDonald CM, Guglieri M, Vučinić D, et al. Long-term evaluation of givinostat in Duchenne muscular dystrophy, and natural history comparisons. Ann Clin Transl Neurol. Published online August 19, 2025. doi:10.1002/acn3.70165

2. ITF Therapeutics announces publication of positive long-term data reinforcing givinostat efficacy and safety as a treatment for Duchenne muscular dystrophy. News Release. ITF Therapeutics. August 25, 2025. Accessed August 29, 2025. https://itftherapeutics.com/documents/ITF-Therapeutics-Announces-Publication-of-Positive-Long-FINAL.pdf