Scott Baver, PhD, Vice President of Medical Affairs at ITF Therapeutics, discusses new data on the use of Duvyzat (givinostat) for patients with Duchenne muscular dystrophy (DMD).
DMD is a rare neuromuscular disorder characterized by progressive muscle wasting. DMD occurs primarily in males, though in rare cases may affect females. The symptoms of DMD include progressive weakness and atrophy of both skeletal and heart muscle. Early signs may include delayed ability to sit, stand, or walk and difficulties learning to speak. DMD is caused by genetic changes in the DMD gene that is involved in the synthesis of dystrophin.
Givinostat is an orally administered histone deacetylase (HDAC) inhibitor that regulates excessive HDAC activity in DMD muscles and restores expression of key genes and biological processes essential for muscle maintenance and repair. It is currently indicated for treatment of patients with DMD ages 6 years and older.
New data on the use of givinostat in patients with DMD was presented at the 2025 Neuromuscular Study Group (NMSG) Annual Scientific Meeting.
Givinostat Weight-based Flexible Dosing: Rationale and Efficacy at the Different Doses
This poster includes an analysis of data on weight-based flexible dosing from the multicenter, randomized, double-blind, placebo-controlled, Phase 3 EPIDYS clinical trial. In this study, patients with DMD received weight-based givinostat dosing plus standard of care (i.e., corticosteroids) at two levels, dose A or B, depending on study protocol. Doses were adjusted (A to B or B to C) based on predefined rules related to tolerability to achieve the highest tolerated dose for each patient. This analysis assesses mean change from baseline in 4-stair climb (4SC) time and total North Star Ambulatory Assessment (NSAA) scores to evaluate efficacy based on the final administered dose at week 72.
A total of 39 patients started at dose A and 42 patients started at dose B. The dose was reduced in 36 patients. Overall, 21 patients received final dose A, 44 dose B, and 16 dose C. Givinostat blood concentrations were similar across all patients and within the range of efficacy. At week 72, the placebo-corrected difference in least squares mean CFB (95% CI) in 4SC time was A: –2.61 (–4.97, –0.26), B:–1.35 (–3.25, 0.54) and C: –1.90 (–4.48, 0.67). For NSAA, the least squares mean change (placebo-corrected) was A: 3.35 (1.07,5.64), B: 1.24 (–0.57, 3.05), and C: 1.94 (–0.58, 4.46). These results were favorable for givinostat over placebo in all 3 doses.
Characterizing Thrombocytopenia in Patients with Duchenne Muscular Dystrophy Treated with Givinostat: Results from the Phase 3 EPIDYS Trial
This analysis further characterizes the risk and severity of thrombocytopenia, a known adverse event of givinostat, or decreased platelet count based on an assessment of data from patients treated with givinostat in the Phase 3 EPIDYS study of 179 boys ages 6 years or older with DMD. A total of 118 patients were assigned to oral givinostat and 61 patients to placebo over 18 months, while continuing standard of care. Thrombocytopenia and decrease in platelet count were assessed.
Overall, 32.2% of givinostat-treated patients experienced thrombocytopenia or decreased platelet count compared with 0 patients receiving placebo. All adverse events of thrombocytopenia/decreased platelet count were grade 1 or 2 in severity, and none resulted in study drug withdrawal. A total of 14.4% and 13.6% of givinostat-treated patients required dose reduction owing to thrombocytopenia or decreased platelet count, respectively. No events of thrombocytopenia or decreased platelet count led to temporary treatment interruption. The median time to platelet count nadir with givinostat was 85.0 days. The median time to platelet count recovery was 26.0 days.
In patients on givinostat treatment, platelet count reductions occur early, and levels recover to normal within 1 month. Although thrombocytopenia/decreased platelet count resulted in dose reductions in 14.4% and 13.6% givinostat-treated patients, respectively, all events were mild or moderate in severity and managed without treatment interruption.
Vastus Lateralis Fat Fraction (VLFF) is Associated with Functional Efficacy Endpoints in Patients with Duchenne Muscular Dystrophy Treated with Givinostat
This poster reports findings from a post-hoc analysis assessing whether changes from baseline in VLFF correlate with measures of disease progression in patients with DMD. The analysis examines VLFF alongside efficacy endpoints observed at the end of the study (month 18), including 4SC, time to rise, 6-minute walking test, and NSAA. Included in the analysis was 77 patients on givinostat and 37 on placebo in addition to standard of care.
Results illustrated a relatively high reciprocal relationship with 4SC, 6-minute walk test, and NSAA. The correlation between VLFF and time to rise was not statistically significant. Based on these results, the observed VLFF in response to treatment with givinostat suggests an
association with efficacy endpoints evaluated in EPIDYS. These findings are consistent with previous studies showing a strong relationship between VLFF and functional measures and suggest that reductions in VLFF are clinically meaningful in patients treated with givinostat.
Givinostat Effect on Respiratory Function in Duchenne Muscular Dystrophy Before and After Ambulation Loss: Results from EPIDYS, LTSE, and PRO-DMD-01 Studies
This poster includes findings previously presented at the 2025 MDA Clinical and Scientific Conference and reports observations on respiratory function in patients who experienced loss of ambulation during follow-up. The analysis indirectly compares forced vital capacity (FVC) %-predicted trajectories from patients treated with givinostat and corticosteroids in the Phase 3 EPIDYS study and its ongoing open-label extension with FVC %-predicted trajectories from patients in a natural history study of DMD disease progression who received corticosteroids only.
The analysis included 56 patients treated with givinostat and steroids compared with published data on 51 patients from the PRO-DMD-01 study who received steroids only. Among weighted givinostat-treated patients, 2 years before loss of ambulation, the weighted least squares mean FVC %–predicted was 91.3%, decreasing to 83.0% at loss of ambulation and 74.4% 2 years post-loss of ambulation. The mean annual decline in FVC %–predicted was 3.6% before loss of ambulation and 3.9% after. In the PRO-DMD-01 study, the mean annual decline in FVC %–predicted was 5.6% before loss of ambulation and increased to 10.1% after.
FVC%–predicted trajectories showed a slower and less pronounced decline in patients treated with givinostat compared with those treated with steroids only, suggesting improved pulmonary function stabilization with givinostat treatment.
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To learn more about DMD and other rare musculoskeletal disorders, visit https://checkrare.com/diseases/musculoskeletal-diseases/