Core Insights - Zorevunersen shows potential as a disease-modifying therapy for Dravet syndrome, demonstrating durable seizure reductions and improvements in cognition, behavior, and quality of life in patients [1][3][4] Clinical Data - Long-term Phase 1/2a and open label extension (OLE) studies indicate significant reductions in seizure frequency and increased seizure-free days for patients treated with zorevunersen alongside standard anti-seizure medicines [1][3][4] - A propensity score weighted analysis revealed that patients receiving zorevunersen experienced statistically significant reductions in major motor seizure frequency at six months, consistent with the ongoing Phase 3 EMPEROR study [5][6] - Improvements in cognition and behavior were observed at 18 months, with several assessments reaching statistical significance [5][6] Mechanism of Action - Analysis of electroencephalogram (EEG) data supports a disease-modifying mechanism of action for zorevunersen, showing dose-dependent effects in decreasing abnormal brain activity associated with Dravet syndrome [2][7] Safety Profile - Zorevunersen has been generally well tolerated, with 30% of patients in Phase 1/2a studies and 53% in OLE studies experiencing treatment-emergent adverse events (TEAEs) [8] - The most common TEAE was CSF protein elevations, occurring in 14% of patients in Phase 1/2a and 45% in OLE studies, with no related clinical manifestations observed [8] Future Directions - The ongoing Phase 3 EMPEROR study aims to further evaluate the efficacy and safety of zorevunersen in children with Dravet syndrome, with a focus on seizure frequency and improvements in behavior and cognition [12] - The collaboration between Biogen and Stoke Therapeutics is expected to advance the development and commercialization of zorevunersen for Dravet syndrome [11][16]