Givinostat is a novel orally active histone deacetylase inhibitor being developed for the treatment of Duchenne muscular dystrophy (DMD). Givinostat efficacy and safety were assessed in the Epidys Study, a randomized, double blind, placebo controlled, multicenter Phase 3 study in ambulant DMD patients (NCT02851797). Study DSC/14/2357/51 (NCT03373968) is an ongoing open label, long-term study of givinostat in 200 DMD male subjects previously enrolled in one of the other DMD givinostat studies who will receive treatment until givinostat marketing approval. The long-term efficacy of givinostat in the treatment of DMD was evaluated by comparing patients enrolled in the Epidys study and study DSC/14/2357/51 to matched patients from ImagingDMD (NCT01484678) and the CINRG (NCT00468832) natural history studies. The age at transition to disease progression milestones (hard binary endpoints used in Kaplan Maier survival analyses) included in the long-term efficacy analyses were the Age at persistent: rise from floor > 10 seconds, 10 m walk/run > 10 seconds, loss of rise from floor ability, loss of 4 standard stairs climb (4SC) ability, and loss of ambulation which was defined as inability to walk 10 meters within 30 seconds. 148 boys treated with givinostat were compared to 197 boys enrolled in the natural history studies treated with steroids. Transition beyond all the specific disease progression milestones were significantly delayed by givinostat treatment (on top of steroid treatment). In particular, in the givinostat-treated patients:
•Median age at first rise from floor > 10 seconds was delayed by 1.7 years (Hazard Ratio, Mean (95%CI) = 0.62 (0.45,0.84); p=0.003).
•Median age at first 10 m walk/run > 10 seconds was delayed by 3.5 years (Hazard Ratio, Mean (95%CI) = 0.43 (0.29, 0.64); p<0.0001). •Median age at loss of rise from floor was delayed by 2.2 years (Hazard Ratio, Mean (95%CI) = 0.68 (0.47,0.97); p=0.034). •Median age at loss of 4 standard stairs climb (4SC) was delayed by 3.3 years (Hazard Ratio, Mean (95%CI) = 0.42 (0.26, 0.67); p<0.0001). •Median age at loss of ambulation was delayed by 2.7 years (Hazard Ratio, Mean (95%CI) = 0.48 (0.27,0.86); p=0.012). In conclusion, these results show that givinostat can delay clinically meaningful DMD disease milestones beyond the expected delays observed with standard of care steroids. These results confirm givinostat efficacy demonstrated in the Epidys Study with longer-term treatment.