Biogen, Stoke Therapeutics present data from studies of zorevunersen

Biogen (BIIB) and Stoke Therapeutics (STOK) announced the presentation of data from an analysis that informed the design of the Phase 3 EMPEROR study and evaluated the potential effects of the Phase 3 zorevunersen dosing regimen. The data are complementary to previously reported data from a broader cohort of patients treated with zorevunersen in the Phase 1/2a and open label extension studies that showed improvements within the first 9 months and continuing improvements through an additional two years. The new analysis is best aligned with the timing and dosing regimen that will be evaluated in the pivotal Phase 3 EMPEROR study and showed improvements in multiple measures of cognition and behavior at Week 68. The results contrasted with findings from a natural history study in which patients with Dravet syndrome were treated with standard of care medicines. Zorevunersen is in development as a first-in-class potential disease modifying treatment for Dravet syndrome. Results were presented as part of the Epilepsy II session at the 16th European Paediatric Neurology Society Congress. Previously presented data from the two Phase 1/2a and OLE studies showed substantial and durable reductions in major motor seizure frequency on top of a background of standard anti-seizure medicines and improvements in multiple measures of cognition and behavior through two years of treatment in the OLE studies. Data indicated responses may be better among patients who were treated with loading doses of 70mg followed by maintenance doses of 45mg. Zorevunersen was generally well-tolerated across these studies. A mixed-effects model for repeated measures analysis was used to evaluate the potential effects of the Phase 3 zorevunersen dosing regimen on patient cognition and behavior at Week 68. The model was developed using clinical data from patients in the Phase 1/2a ADMIRAL study and the LONGWING OLE study. An analysis of patients who received a total cumulative dose consistent with the Phase 3 EMPEROR regimen of two loading doses of 70mg followed by two maintenance doses of 45mg, showed improvements in cognition and behavior. The analysis was performed to inform the design of the Phase 3 EMPEROR study. Baseline covariates for patients followed in the BUTTERFLY natural history study were matched to the selected ADMIRAL patient population. Improvements in patients treated with zorevunersen contrasted with findings from BUTTERFLY. These data support the selection of five sub-domains of the Vineland-3 Adaptive Behavior Scales, including Receptive Communication, Expressive Communication, Interpersonal Relationships, Coping Skills, and Personal Skills now under evaluation as key secondary endpoints in the Phase 3 EMPEROR study.