Background: The safety and efficacy of givinostat were evaluated in the phase 3 EPIDYS study (NCT02851797). An ongoing open-label extension (OLE) is evaluating the long-term safety, tolerability, and efficacy of givinostat in patients with Duchenne muscular dystrophy (DMD) who completed, or were screened but not randomized, in prior givinostat studies (NCT03373968).
Objective: This interim analysis aimed to characterize the safety data observed to date in the OLE.
Results: As of the December 31, 2023 data cutoff, 207 patients have enrolled: givinostat (n=119; mean [SD] age: 11.6 [2.1] y), received placebo in prior study (delayed givinostat: n=58; 11.5 [2.1] y), and not included in prior study (naïve givinostat: n=30; 10.5 [2.3] y) groups. All patients received weight-based givinostat and corticosteroids. Safety data were evaluated for patients who received ≥1 dose of givinostat. The mean (SD) duration of givinostat exposure was 1256.0 (522.9), 1134.9 (346.4), and 1073.7 (260.2) days in the givinostat, delayed givinostat, and naïve givinostat groups, respectively. Overall, 98.1% of patients reported ≥1 treatment-emergent adverse event (TEAE; 2793 events), with similar incidence among groups. Most TEAEs were mild (2294 events) or moderate (445 events). Among TEAEs reported in ≥10% of the overall population, diarrhea occurred more often in the delayed givinostat (36.2%) and naïve givinostat (36.7%) groups compared with the givinostat group (27.7%). More falls were reported by the givinostat (31.9%) and naïve givinostat (33.3%) groups compared with delayed givinostat (10.3%). Reports of thrombocytopenia were higher in the delayed givinostat (24.1%) compared with the givinostat (14.3%) and naïve givinostat (13.3%) groups. The givinostat group reported pyrexia (29.4%), increased blood triglycerides (18.5%), and decreased platelet count (12.6%); corresponding rates in the delayed givinostat group were 24.1%, 19.0%, and 19.0%, and in the naïve givinostat group were 13.3%, 40.0%, and 10.0%. Decreased platelets and increased triglycerides (first 2 to 4 weeks of treatment) were followed by stabilization in the delayed and naïve givinostat groups; levels remained stable for the givinostat group.
Conclusions: These results align with the known safety profile of givinostat. Early decreases in platelets and increases in triglycerides, consistent with treatment initiation, stabilized over time. No new safety signals emerged in patients continuing givinostat.