Long-Term Safety of Givinostat in Patients With Duchenne Muscular Dystrophy: Results From an Open-Label Extension Study

Topic:

Clinical Trials

Poster Number: P275

Author(s):

John Brandsema, MD, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Gyula Acsadi, MD, PhD, Connecticut Children's Medical Center, Nicoletta Coceani, MSc, Italfarmaco SpA, Federica Alessi, Italfarmaco SpA., Sara Cazzaniga, Msc, Italfarmaco SpA., Paolo Bettica, MD, PhD, Italfarmaco SpA., Erika L Finanger, MD, MS, Oregon Health and Science University

Background: Givinostat, an oral histone deacetylase inhibitor, was recently approved for Duchenne muscular dystrophy (DMD) treatment in patients aged 6 years and older.

Objectives: This study evaluated safety data from the ongoing open-label, long-term safety, tolerability, and efficacy study of givinostat in boys (NCT03373968) who completed or were screened but not randomized in previous DMD givinostat studies and agreed to enter this study.

Results: As of the December 31, 2021 data cutoff, 194 patients have enrolled: givinostat (n=110), prior placebo (n=54), and not included in prior study (n=30) groups. All patients received givinostat and corticosteroids during this study. Safety data were evaluated for patients who received at least one givinostat administration. The mean duration of givinostat exposure was 616, 506, and 451 days in the givinostat, prior placebo, and not-included groups, respectively. Overall, 87.1% of patients reported at least one treatment-emergent adverse event (TEAE), with similar incidence among all groups. Most TEAEs were mild to moderate in severity. Among the most frequently reported TEAEs (at least 10% of the overall population), diarrhea was reported more frequently by the prior placebo (27.8%) and not-included (36.7%) groups compared with the givinostat group (18.2%). More falls were reported by the givinostat group (20.0%) compared with the prior placebo (9.3%) and not-included (13.3%) groups. More reports of thrombocytopenia were observed in the prior placebo group (20.4%) compared with the givinostat (9.1%) and not-included (10.0%) groups. The givinostat group reported pyrexia (17.3%), increased blood triglycerides (12.7%), and decreased platelet count (9.1%); in comparison, the incidence of these TEAEs in the prior placebo group was 13.0%, 16.7%, and 14.8%, respectively, and 6.7% for each TEAE in the not-included group. Decreased platelets and increased triglycerides followed by stabilization are consistent with givinostat treatment initiation.

Conclusions: These results are consistent with the known safety profile of givinostat. No new safety signals were observed in patients continuing givinostat.