CAMBRIDGE, Mass. and BEDFORD, Mass. — Biogen Inc. (Nasdaq: BIIB) and Stoke Therapeutics, Inc. (Nasdaq: STOK), 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.
Details of the AES Presentations:
- Title: Zorevunersen Continues to Demonstrate Potential as a Disease-modifying Therapy in Long-term Open-label Extension Studies of Patients with Dravet Syndrome
Oral Presentation Date & Time: Friday, December 5, 3:30-5:55 PM EST
Oral Presenter: 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
- Title: Zorevunersen Demonstrates Disease-modifying Potential in Patients with Dravet Syndrome with Increases in Seizure-free Days, Improvements in Quality of Life, and Benefits in Overall Clinical Status
Poster Presentation Date & Time: Saturday, December 6, 12:00-2:00 PM EST
Poster Presenter: Kelly Knupp, M.D., MSCS, Professor of Pediatrics and Neurology at the University of Colorado Anschutz and the Dravet Program Director and Epilepsy Program Lead at Children’s Hospital Colorado
Poster Number: 1.379
- Title: Zorevunersen Continues to Demonstrate Potential as a Disease-modifying Therapy in Long-term Open-label Extension Studies of Patients with Dravet Syndrome
Poster Presentation Date & Time: Sunday, December 7, 12:00-2:00 PM EST
Poster Presenter: 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
Poster Number: 2.341
- Title: Spectral Electroencephalogram Abnormalities Across Development in Patients with Dravet Syndrome
Poster Presentation Date & Time: Sunday, December 7, 12:00-2:00 PM EST
Poster Presenter: Pieter van Mierlo, Founder and Chief Scientific Officer, Epilog, Clouds of Care, Associate Professor, Ghent University
Poster Number: 2.432
- Title: Electrophysiological Improvements in Patients with Dravet Syndrome Following Treatment with Zorevunersen, an Investigational Antisense Oligonucleotide
Poster Presentation Date & Time: Monday, December 8, 12:00-1:45 PM EST
Poster Presenter: Nigel Colenbier, Senior Data Scientist, Epilog, Clouds of Care
Poster Number: 3.489
About Dravet Syndrome
Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by recurrent seizures as well as significant cognitive and behavioral impairments. Most cases of Dravet are caused by mutations in one copy of the SCN1A gene, leading to insufficient levels of NaV1.1 protein in neuronal cells in the brain. Even when treated with the best available anti-seizure medicines (ASMs), up to 57 percent of patients with Dravet syndrome do not achieve ≥50 percent reduction in seizure frequency. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Developmental and cognitive impairments often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP; up to 20 percent of children and adolescents with Dravet syndrome die before adulthood due to SUDEP, prolonged seizures, seizure-related accidents or infections1. Dravet syndrome occurs globally and is not concentrated in a particular geographic area or ethnic group. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the U.S. (~16,000), UK, EU-4 and Japan. 2 There are no approved disease-modifying therapies for people living with Dravet syndrome.
About Zorevunersen
Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing functional NaV1.1 protein production in brain cells from the non-mutated (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition, and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function, in the SCN1A gene. Stoke has a strategic collaboration with Biogen to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights.
About the EMPEROR Study
The EMPEROR Phase 3 Study (NCT06872125) is a global, double-blind, sham-controlled study evaluating the efficacy, safety, and tolerability of zorevunersen in children ages 2 to <18 with Dravet syndrome with a confirmed variant in the SCN1A gene not associated with gain-of-function. The trial is currently enrolling patients within the United States and is expected to enroll participants across Japan, United Kingdom and European Union, with participants being randomized 1:1 to receive either zorevunersen via intrathecal administration or a sham comparator for a 52-week treatment period following an 8-week baseline period. Following the completion of the study, eligible participants will be offered ongoing treatment with zorevunersen as part of an OLE study. The primary endpoint of the study is percent change from baseline in major motor seizure frequency at week 28 in patients receiving zorevunersen as compared to sham. The key secondary endpoints are the durability of effect on major motor seizure frequency and improvements in behavior and cognition as measured by Vineland-3 subdomains, including expressive communication, receptive communication, interpersonal relationships, coping skills and personal skills. Additional endpoints include safety, Clinician Global Impression of Change (CGI-C), Caregiver Global Impression of Change (CaGI-C), and the Bayley Scales of Infant Development (BSID-IV). For more information, visit https://www.emperorstudy.com/.
About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media – Facebook, LinkedIn, X, YouTube.
About Stoke Therapeutics
Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts. For more information, visit https://www.stoketherapeutics.com/.
References
- Symonds, J. et al. Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants. Brain. 2021;144(9):2879-2891.
- Based on Stoke Therapeutics’ preliminary estimates, which scaled annual incidence to prevalence using country-specific live birth rates over the past 85 years and adjusted for Dravet-specific mortality. The estimate is based on incidence rates published by Wu et al., Pediatrics, 2015.
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