Stoke Therapeutics and Biogen Present Long-Term Zorevunersen Data Supporting Potential Disease-Modifying Treatment for Dravet Syndrome
Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company focused on restoring protein expression through RNA medicine, and Biogen Inc. (Nasdaq: BIIB) have announced the presentation of new clinical data for zorevunersen at the 16th European Epilepsy Congress (EEC), being held September 5–9, 2026, in Athens, Greece. The latest findings add to a growing body of clinical evidence evaluating zorevunersen as a potential first-in-class disease-modifying treatment for Dravet syndrome, a rare and severe genetic form of epilepsy associated with recurrent seizures and significant developmental, cognitive, and behavioral challenges.
The data presented at the congress include more than five years of clinical experience with zorevunersen in people living with Dravet syndrome. The evidence comes from two Phase 1/2a studies and ongoing open-label extension (OLE) studies. According to the companies, the longer-term results demonstrate sustained reductions in seizures as well as continuing improvements in cognition and behavior.
Additional exploratory analyses presented at EEC provide further insight into the potential impact of treatment. One analysis showed substantial reductions in some of the most severe seizure types associated with Dravet syndrome, including generalized tonic-clonic and focal-to-bilateral tonic-clonic seizures. These seizure types are particularly concerning because they are associated with increased morbidity and mortality and are among those most strongly correlated with sudden unexpected death in epilepsy, or SUDEP.
Another analysis found substantial improvements in quality of life through 28 months of treatment in the open-label extension studies. Zorevunersen has also continued to be generally well tolerated in the ongoing studies, with some patients now having received treatment for more than five years.
Dravet Syndrome Extends Beyond Seizure Control
Dravet syndrome is a severe developmental and epileptic encephalopathy that typically begins during infancy or early childhood. While seizures are one of its most visible clinical manifestations, the disorder can affect multiple aspects of neurological development and daily life.
Children with Dravet syndrome may experience cognitive impairment, behavioral difficulties, developmental delays, communication challenges, and limitations in their ability to perform everyday activities independently. As a result, the burden of the disease extends well beyond seizure frequency.
The long-term zorevunersen findings are therefore significant because they suggest potential effects across several dimensions of the disease rather than focusing exclusively on seizure reduction.
Helen Cross, MB ChB, Ph.D., Professor, The Prince of Wales’s Chair of Childhood Epilepsy and Director of University College London Great Ormond Street Institute of Child Health, as well as Honorary Consultant in Paediatric Neurology at Great Ormond Street Hospital, emphasized the broader impact of Dravet syndrome.
“Seizures are the most acute symptom of Dravet syndrome but the disease affects nearly every aspect of a child’s development, from their ability to communicate with loved ones to skills like dressing and feeding themselves,” Cross said.
She noted that the continued improvements in cognition and behavior observed in the studies could potentially help reduce the developmental gap between children with Dravet syndrome and their neurotypical peers. Improved functioning could potentially support greater independence and participation in activities that might otherwise be difficult for affected children.
Four-Year Open-Label Extension Data
The four-year OLE results provide some of the longest-term clinical experience reported for zorevunersen.
Following participation in the Phase 1/2a studies, 93%, or 75 of 81 eligible patients, continued into the open-label extension studies. At the four-year data cutoff, 77%, or 58 of those 75 patients, remained enrolled.
Patients receiving zorevunersen in addition to their standard anti-seizure medicines continued to demonstrate durable seizure reductions. At the same time, investigators reported ongoing improvements in cognition and behavior.
Statistically significant improvements in cognition and behavior were observed at one, two, three, and four years of treatment compared with the OLE baseline.
These findings are particularly important for a condition such as Dravet syndrome, where controlling seizures is only one component of managing the disease. The possibility of sustained improvements in neurodevelopmental measures could represent a meaningful advancement if confirmed in larger controlled studies.
The continued participation of patients in the long-term extension program also allows investigators to accumulate additional information about the durability of treatment effects and the longer-term safety profile of zorevunersen.
Reduction in Severe Seizures
The EEC presentation also included a new exploratory analysis focused on severe seizure types.
People with Dravet syndrome frequently experience seizures that can be prolonged, difficult to control, and resistant to available therapies. The condition is also associated with a substantially higher risk of SUDEP compared with the broader epilepsy population.
Generalized tonic-clonic seizures, focal-to-bilateral tonic-clonic seizures, and tonic-clonic seizures of unknown origin are considered among the most severe seizure categories and are associated with significant morbidity and mortality in people with epilepsy.
In the zorevunersen open-label extension studies, patients demonstrated substantial reductions in generalized tonic-clonic and focal-to-bilateral tonic-clonic seizures through three years compared with the Phase 1/2a baseline.
The findings are particularly relevant because reducing seizure frequency alone does not necessarily capture the full clinical value of a treatment for Dravet syndrome. Severe seizure reduction may have implications for patient safety and quality of life, although further controlled clinical research will be necessary to determine the extent to which these findings translate into reductions in serious complications or mortality.
Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics, highlighted the importance of the severe seizure findings.
“These data are especially meaningful because they show substantial reductions in the severe seizures most strongly correlated with SUDEP and demonstrate continuing improvements in the debilitating neurodevelopmental aspects of the disease,” Ticho said.
He added that the quality-of-life improvements observed in the studies further increase the company’s confidence in the potential role of zorevunersen for the Dravet syndrome community.
Quality of Life Improvements
Beyond seizure and neurological measures, researchers also evaluated the potential impact of zorevunersen on quality of life.
An exploratory analysis demonstrated substantial improvements in quality of life through 28 months in the OLE studies compared with the Phase 1/2a baseline.
The analysis used the EuroQol Visual Analog Scale (EQ-VAS), a component of the EuroQol-5D Youth assessment. EQ-VAS is a validated measure of overall health status that ranges from 0 to 100, with higher scores representing better perceived health.
Quality of life is an important consideration in chronic neurological disorders because treatment success can involve more than changes in clinical measurements. For children and adolescents with Dravet syndrome, improvements in health status can potentially affect communication, mobility, independence, family activities, education, and everyday participation.
The reported improvements therefore provide another perspective on the potential real-world impact of zorevunersen.
Long-Term Safety Experience
Safety and tolerability remain important considerations for any potential long-term treatment for a chronic pediatric neurological disease.
According to the companies, zorevunersen continues to be generally well tolerated in the Phase 1/2a and ongoing OLE studies. Some participants have now received treatment for more than five years.
As of July 31, 2026, more than 930 doses of zorevunersen had been administered across the clinical program.
One laboratory finding observed during treatment involved elevated cerebrospinal fluid (CSF) protein levels. Approximately 94% of patients experienced elevated CSF protein laboratory values, and 59% of these cases were classified as treatment-emergent adverse events.
Importantly, the companies reported that no serious or severe clinical manifestations have been associated with these CSF protein elevations. There have also been no reported cases of hydrocephalus.
Continued long-term monitoring will remain important as the clinical program advances, particularly given the chronic nature of Dravet syndrome and the potential for treatment to begin early in life and continue for many years.
Stephanie Fradette, Pharm.D., Head of the Rare Neurology Development Unit at Biogen, emphasized the importance of continued safety monitoring.
“For patients with a chronic disease like Dravet syndrome, safety and tolerability are critically important,” Fradette said.
She noted that the ongoing open-label extension studies will continue contributing to the understanding of zorevunersen’s long-term safety and its potential to address the underlying genetic cause of Dravet syndrome.
Phase 3 EMPEROR Study Advances
The long-term findings arrive as Stoke Therapeutics and Biogen advance zorevunersen through the pivotal Phase 3 development program.
The global Phase 3 EMPEROR study is currently underway to evaluate the efficacy and safety of zorevunersen. Enrollment has been completed in the planned primary analysis population, which includes 162 patients enrolled in the United States, United Kingdom, and Japan.
The primary analysis is designed to compare zorevunersen with sham treatment, with both administered through lumbar puncture.
Enrollment in Europe has also been completed, with 34 participants enrolled.
A Phase 3 data readout is anticipated in the third quarter of 2027. The companies expect these results to support completion of a planned rolling New Drug Application submission to the U.S. Food and Drug Administration during the second half of 2027.
The outcome of the EMPEROR study could represent an important milestone in determining whether the clinical benefits observed in earlier studies can be confirmed in a larger controlled population.
Potential Disease-Modifying Approach
Zorevunersen is being developed as a potential disease-modifying therapy rather than solely as another treatment for seizure control.
Stoke Therapeutics’ RNA medicine approach is designed to harness the body’s natural cellular machinery to restore protein expression. In Dravet syndrome, the disease is commonly associated with pathogenic variants affecting the SCN1A gene, which plays an important role in neuronal function.
The goal of zorevunersen development is to address the underlying genetic mechanism and potentially restore sufficient protein expression to improve neurological function.
If successful, such an approach could represent a meaningful shift in how Dravet syndrome is treated. Current management generally focuses on controlling seizures and addressing associated developmental and behavioral challenges, whereas a disease-modifying treatment could potentially influence multiple aspects of the disorder.
The five-plus years of clinical experience presented at EEC provide encouraging evidence regarding the durability of zorevunersen’s effects, particularly the reported seizure reductions and continuing cognitive and behavioral improvements. However, the Phase 3 EMPEROR study remains critical for establishing the therapy’s efficacy and safety in a larger, controlled clinical setting.
The latest EEC findings reinforce the potential importance of developing treatments that address the broader burden of Dravet syndrome. Sustained seizure reduction, improvements in cognition and behavior, enhanced quality of life, and a manageable long-term safety profile could collectively represent meaningful benefits for patients and their families.
The reduction in severe seizure types is particularly noteworthy given the relationship between these seizures and serious outcomes such as SUDEP. At the same time, continued improvements in cognitive and behavioral measures suggest that zorevunersen may have the potential to address aspects of Dravet syndrome that extend beyond seizure control.
With enrollment completed in key populations of the Phase 3 EMPEROR study and a data readout anticipated in the third quarter of 2027, the development program is entering a decisive stage.
For families affected by Dravet syndrome, a condition that can profoundly alter childhood development and carry significant lifelong risks, the possibility of a therapy capable of addressing the underlying genetic cause represents an important area of research.
Stoke Therapeutics and Biogen will continue evaluating zorevunersen through the ongoing Phase 3 program and long-term extension studies. The results of these investigations will help determine whether the promising observations from early-stage and open-label studies can ultimately translate into a new treatment option for people living with Dravet syndrome.
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 infections3. 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 Japan4. 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 unaffected (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, and China’s Center for Drug Evaluation has granted zorevunersen Breakthrough Therapy Designation.
Stoke has a strategic collaboration with Biogen (Nasdaq: BIIB) 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. Zorevunersen is currently in clinical development, and its safety and efficacy have not been evaluated by any regulatory authority.
About the Phase 1/2a and Open-Label Extension Studies
Two Phase 1/2a open-label, multicenter studies evaluated the effects of zorevunersen in patients with highly refractory Dravet syndrome ages 2 to 18 years (N=81). Primary endpoints were the safety profile, plasma pharmacokinetics (PK) and exposure in cerebrospinal fluid (CSF) of single and multiple doses of zorevunersen. Secondary endpoints included percentage change from baseline in major motor seizure frequency, overall clinical status (a measure of patients’ overall functioning) and quality of life.
The ADMIRAL Phase 1/2a study included an exploratory endpoint to evaluate changes in neurodevelopmental status (cognition & behavior) as measured by Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). The Phase 1/2a studies were completed in November 2023. Following treatment in the Phase 1/2a studies, eligible patients continued treatment with zorevunersen every four months in one of two OLEs. There was at least a 6-month gap between the last dose administered in the Phase 1/2a studies and the first dose administered in the OLEs.
The primary endpoints are the safety profile of multiple doses of zorevunersen. Secondary endpoints include PK parameters, percentage change from baseline in major motor seizure frequency, change in overall clinical status, and change from baseline in quality of life. Exploratory endpoints include changes in neurodevelopment status as measured by Vineland-3. Results from the Phase 1/2a and OLE studies were published in The New England Journal of Medicine (NEJM) in March 2026. The OLE studies are ongoing.
About the Phase 3 EMPEROR Study
The Phase 3 EMPEROR 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. Stoke completed enrollment in the United States, United Kingdom and Japan in June 2026, and a data readout is anticipated in the third quarter of 2027 to support the submission of a rolling New Drug Application (NDA) to the FDA. Enrollment in Europe completed in August 2026. Enrollment is currently underway in China and is anticipated to complete in the second half of 2026.
Participants in EMPEROR are 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 treatment period, eligible participants will be offered ongoing treatment with zorevunersen as part of an open-label period of the 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://clinicaltrials.gov/study/NCT06872125.
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/ or follow us on LinkedIn.
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.