G.O.23

A clinical trial programme to assess safety and efficacy of drisapersen (DRIS) in DMD comprises two Phase 2, one Phase 3 placebo (PBO)-controlled, (total N  = 290) and two open-label extension (OLE) trials ( N  = 233). The Phase 2 studies enrolled comparable populations with relatively mild disease (mean baseline [BL] 6-min walking distance [6MWD] ∼400 m). At Wk 25, DMD114117 (117; N  = 53) showed a statistically significant and clinically meaningful treatment difference of +35 m ( p  = 0.014) in 6MWD for 6 mg/kg/wk continuous DRIS treatment vs PBO (maintained at Wk 49 [+36 m; p  = 0.051]); %-predicted 6MWD improved by 6% ( p N  = 51), a clinically meaningful treatment difference was seen in 6MWD (+27 m; p  = 0.069); %-predicted 6MWD improved by 5% ( p  = 0.051). The Phase 3 study DMD114044 (044; N  = 186) enrolled a more severe population (mean BL 6MWD  p  = 0.048) for DRIS 6 mg/kg/wk vs. PBO. At 96 wks in the OLE fed by 117 and 044, the treatment difference ( n  = 113) was +46 m from BL for continuous 6 mg/kg DRIS vs starting DRIS treatment after 48 wks. In the Phase 1/2 OLE DMD114673 ( n  = 10; average age: 12.9 y), the mean change in 6MWD at Wk 177 (3.4 y) was −24.5 m (median +7.5 m) from OLE BL. Most common AEs with DRIS treatment were injection-site reactions, mild reversible proteinuria. Infrequent moderate to severe thrombocytopenia was also seen. The results of the trial programme are promising, as deterioration of muscle function is associated with the natural history of DMD in young boys. Overall, observed improvements or reductions in decline in 6MWD over 24–96 wks at this stage of the disease is indicative of an encouraging effect in reducing disease progression.