Biogen and Stoke Present New Data Supporting Zorevunersen’s Disease-Modifying Potential in Dravet Syndrome at AES 2025
Biogen and Stoke Therapeutics, a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today announced data presentations that further support the potential of zorevunersen, an investigational antisense oligonucleotide, as a disease-modifying medicine for Dravet syndrome. These data were presented at the 2025 American Epilepsy Society (AES) Annual Meeting in Atlanta, Georgia.
Long-term results from the ongoing Phase 1/2a and open label extension (OLE) studies demonstrated durable seizure reductions, including increases in seizure-free days, in addition to improvements in cognition, behavior and quality of life in patients treated with zorevunersen on top of standard of care anti-seizure medicines (ASMs). A new propensity score weighted analysis provides the first direct comparison between patients with Dravet syndrome treated with zorevunersen and a matched cohort from the BUTTERFLY natural history study and showed reductions in seizures and improvements in cognition and behavior with dose levels and timepoints similar to and consistent with the ongoing Phase 3 EMPEROR study.
“Over the last four years we have gained an increasing appreciation for the potential to change the course of Dravet syndrome with new disease-modifying medicines. Open-label data from the zorevunersen clinical studies have been highly encouraging, bringing hope and anticipation to the Dravet community,” said M. Scott Perry, M.D., Head of Neurosciences and Director of the Jane and John Justin Institute for Mind Health and Medical Director of the Genetic Epilepsy Clinic at Cook Children’s Medical Center. “In addition, the new propensity score weighted analysis comparing zorevunersen treatment to patients treated with the current standard of care gives us further context for the improvements we’re seeing in patients living with this devastating disease.”
Propensity Score Weighted Analysis
A propensity score weighted analysis, designed to mimic randomization by adjusting for baseline differences between treated and untreated (natural history) patient groups, showed patients receiving two loading doses of zorevunersen (70mg) experienced statistically significant reductions in major motor seizure frequency at six months compared to natural history. Six months is consistent with the Week 28 Phase 3 primary endpoint measuring the effects of zorevunersen on seizure frequency.
With continued dosing at 45mg, improvements in five key assessments of cognition and behavior as measured by Vineland-3 were shown at 18 months, with several reaching statistical significance. At the 18-month timepoint, cumulative dosing is similar to and consistent with a key secondary endpoint in the Phase 3 EMPEROR study. Durable effects were demonstrated through 24 months, the longest evaluable timepoint in the BUTTERFLY natural history study.
“Data from this analysis, which allows us to match patients treated with zorevunersen directly to natural history, add to a growing body of information shaping our understanding of Dravet syndrome and the effects of zorevunersen over time,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “As we continue to progress our Phase 3 EMPEROR program and await safety and efficacy data from this larger, sham-controlled study, results presented at AES give us additional confidence in what zorevunersen may one day offer to patients and their families.”
“In addition to these important efficacy findings, we are also encouraged by the accumulating long-term safety data, with some patients treated with up to 15 doses over more than four years,” said Katherine Dawson, M.D., Head of the Therapeutics Development Unit at Biogen. “The totality of clinical data, in addition to the new EEG findings, demonstrates zorevunersen’s potential to restore protein function and address the underlying cause of Dravet syndrome to improve debilitating symptoms like seizures and cognitive impairment.”
Electroencephalogram (EEG) Results
Data from an analysis of EEGs performed in patients treated with zorevunersen highlighted the dose-dependent effects of zorevunersen in decreasing abnormal brain activity that is persistently higher in patients with Dravet syndrome. The analysis also showed that a reduction in abnormal EEG activity in the brain was associated with an increased probability of achieving a meaningful reduction in seizure frequency.
Summary of Zorevunersen Safety Data
Eighty-one patients received at least one dose of zorevunersen and have been evaluated for safety, and more than 800 doses have been administered to date. Zorevunersen has been generally well tolerated across the Phase 1/2a and OLE studies. Study drug related treatment emergent adverse events (TEAEs) were observed in 30% (24/81) and 53% (40/75) of patients treated in the Phase 1/2a and OLE studies, respectively. The most common study drug related TEAE was CSF protein elevations reported in 14% (11/81) of patients in the Phase 1/2a studies and 45% (33/75) of patients in the OLE studies.
CSF protein elevations (>50 mg/dL) occurred in 42% (34/81) of patients in the Phase 1/2a studies and 86% (62/72) of patients in the OLE studies. No related clinical manifestations have been observed although one patient discontinued treatment due to elevated CSF protein levels. Treatment-emergent serious adverse events (TESAEs) were reported in 22% (18/81) and 29% (22/75) of patients in the Phase 1/2a and OLE studies, respectively, all of which were assessed to be unrelated to zorevunersen except one patient who experienced SUSARs. Three patient deaths have been reported across the Phase 1/2a and OLE studies, two from sudden unexpected death in epilepsy (SUDEP) and one from malnutrition. All were unrelated to zorevunersen.
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