BEDFORD, Mass.– Stoke Therapeutics, Inc. (Nasdaq: STOK) and Biogen Inc. (Nasdaq: BIIB) presented new long-term data at the 54th Child Neurology Society (CNS) Annual Meeting supporting the potential of zorevunersen as a disease-modifying therapy for Dravet syndrome. The findings, from ongoing open-label extension studies, highlight sustained improvements in cognition, behavior, and overall clinical status among patients receiving zorevunersen.
Two-year data from an analysis designed to evaluate the Phase 3 zorevunersen dosing regimen showed continued gains in cognition and behavior, contrasting sharply with minimal change seen in natural history studies of Dravet syndrome patients on standard of care. Three-year data also showed that 95 percent of clinicians and caregivers reported improvements in overall clinical status, according to Clinical and Caregiver Global Impression of Change (CGI-C and CaGI-C) scales.
“Data from the ongoing open-label extension studies are helping to shape our understanding of the long-term effects of zorevunersen on seizures, cognition, behavior, and overall functioning, which together support the potential for disease modification,” said Kelly Knupp, M.D., MSCS, Professor of Pediatrics and Neurology at the University of Colorado Anschutz and Director of the Dravet Program and Epilepsy Program Lead at Children’s Hospital Colorado. “The natural history data continue to provide important context for the effects we are seeing in patients treated with zorevunersen. Improvements in cognition and behavior are not something we see in patients with Dravet syndrome, and rarely do we see such strong correlation between caregiver and clinician-reported outcomes. Together, these data are starting to paint a fuller picture of the potential impact disease modification could have on a patient’s overall health and daily living.”
The findings were included in a broader poster presentation summarizing data from the Phase 1/2a and ongoing open-label extension studies. While safety and tolerability remained the primary endpoints, secondary analyses assessed effects on major motor seizure frequency, cognition, and behavior. Previously reported results demonstrated durable seizure reduction and cognitive-behavioral improvement over three years, particularly among patients receiving a 70 mg loading dose followed by 45 mg maintenance doses — the regimen now under evaluation in the Phase 3 EMPEROR trial.
Safety data from 81 patients who received at least one dose of zorevunersen indicated that the drug was generally well tolerated. Study-related treatment-emergent adverse events (TEAEs) occurred in 30 percent of Phase 1/2a participants and 53 percent in the open-label extension group. The most common related event was cerebrospinal fluid (CSF) protein elevation, observed in 14 percent and 44 percent of patients, respectively. Elevated CSF protein levels (>50 mg/dL) were found in 42 percent of Phase 1/2a participants and 86 percent of those in the open-label studies. No clinical symptoms associated with these elevations were reported, though one patient discontinued treatment due to elevated CSF protein. Treatment-emergent serious adverse events (TESAEs) occurred in 22 percent and 29 percent of patients in the Phase 1/2a and open-label studies, respectively; all were considered unrelated to the study drug except for a single case involving a suspected unexpected serious adverse reaction (SUSAR).
The accumulating body of evidence from long-term follow-up continues to underscore the promise of zorevunersen as a potential first disease-modifying treatment for Dravet syndrome.
