Stoke and Biogen Share New Zorevunersen Data in Dravet Syndrome
Stoke Therapeutics and Biogen have announced new long-term clinical data that continue to strengthen the evidence supporting zorevunersen as a potential first-in-class disease-modifying therapy for Dravet syndrome. The data were presented during multiple sessions at the 2025 American Epilepsy Society (AES) Annual Meeting, held in Atlanta, Georgia, and include results from ongoing Phase 1/2a studies, open-label extension (OLE) trials, and advanced electroencephalogram (EEG) analyses.
Zorevunersen is an investigational antisense oligonucleotide designed to restore normal protein production in patients with Dravet syndrome by targeting the underlying genetic cause of the disease. Dravet syndrome is a rare and severe form of developmental and epileptic encephalopathy typically beginning in infancy, characterized by frequent, treatment-resistant seizures, cognitive impairment, behavioral challenges, and high mortality risk.
According to the companies, patients treated with zorevunersen in combination with standard-of-care anti-seizure medicines (ASMs) experienced meaningful and sustained reductions in seizure frequency, including increases in seizure-free days. In addition to seizure control, patients demonstrated long-term improvements in cognition, behavior, and overall quality of life—outcomes that are considered critically important in this devastating neurological disorder.
One of the most notable advances presented at AES was a new propensity score weighted analysis comparing zorevunersen-treated patients to a matched group from the BUTTERFLY natural history study. This analysis represents the first direct comparison between patients receiving zorevunersen and those receiving current standard-of-care therapy alone, offering powerful context for interpreting long-term clinical benefits.
Over the last several years, open-label clinical experience with zorevunersen has steadily expanded. Investigators reported that patients receiving two initial loading doses of 70 mg followed by maintenance dosing of 45 mg showed statistically significant reductions in major motor seizure frequency as early as six months after treatment initiation. This six-month timepoint is aligned with the primary endpoint of the ongoing Phase 3 EMPEROR clinical trial currently evaluating the safety and efficacy of zorevunersen in a larger patient population.
Beyond seizure reduction, the propensity score weighted comparison demonstrated significant and sustained improvements in multiple domains of cognition and behavior. These outcomes were measured using five key subscales of the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), one of the most widely accepted tools for evaluating adaptive functioning in patients with neurodevelopmental disorders. At 18 months, patients treated with zorevunersen achieved statistically significant improvements across several domains, including communication, daily living skills, and socialization. Importantly, these benefits remained durable through 24 months, the longest evaluable timepoint in the BUTTERFLY study.
Clinicians participating in the trials emphasized that these cognitive and behavioral gains are particularly meaningful in Dravet syndrome, where progressive developmental impairment places a heavy burden on patients, caregivers, and healthcare systems. Meaningful improvements in daily functioning can translate into greater independence, reduced caregiving demands, and enhanced social engagement for affected families.
“The data presented at AES provide compelling evidence that zorevunersen may not only reduce seizures but also positively influence developmental outcomes in children with Dravet syndrome,” said M. Scott Perry, M.D., Head of Neurosciences and Director of the Jane and John Justin Institute for Mind Health at Cook Children’s Medical Center. “Over the past four years, we have witnessed encouraging progress in these patients. The open-label results continue to strengthen hopes that disease modification is achievable in this historically relentless condition.”
Dr. Perry also highlighted the importance of the natural history comparison. “By comparing patients receiving zorevunersen to those managed on standard therapy alone, we gain a much clearer understanding of the true therapeutic impact we are seeing. The magnitude and durability of improvements we observed provide valuable context for families and clinicians alike.”
Stoke Therapeutics’ Chief Medical Officer, Barry Ticho, M.D., Ph.D., emphasized that the growing clinical dataset is helping reshape scientific understanding of Dravet syndrome itself. “This analysis contributes to an expanding body of real-world and clinical evidence that is enhancing how we view the disease and its progression,” he said. “As the Phase 3 EMPEROR trial progresses, the totality of evidence presented at AES offers us growing confidence in the transformative potential of zorevunersen.”
Biogen executives echoed this optimism while also pointing to the increasingly robust safety database for the therapy. Katherine Dawson, M.D., Head of Biogen’s Therapeutics Development Unit, noted that some patients in the studies have now received up to 15 doses of zorevunersen over more than four years of continuous treatment. “The accumulating long-term safety profile, combined with consistent clinical benefits and emerging EEG findings, strongly supports the hypothesis that zorevunersen may address the root cause of Dravet syndrome,” Dawson said. “The potential to restore protein function rather than simply suppress symptoms represents a fundamentally new treatment paradigm for this patient population.”
Electrophysiological data presented at AES provided further biological validation of this hypothesis. Detailed EEG analyses showed that zorevunersen produced dose-dependent reductions in abnormal brain activity, which is persistently elevated in patients with Dravet syndrome. Investigators reported that decreases in these pathological EEG patterns were associated with an increased probability of achieving meaningful seizure reduction. These findings suggest that zorevunersen may be altering the underlying disease mechanism rather than acting solely as a symptomatic anti-epileptic medication.
The safety profile of zorevunersen was also comprehensively reviewed. A total of 81 patients have now received at least one dose and have been evaluated for safety, with more than 800 doses administered across the Phase 1/2a and OLE studies. Zorevunersen has generally been well tolerated over long-term follow-up. Treatment-emergent adverse events considered related to the study drug were observed in approximately 30% of patients in the Phase 1/2a studies and 53% in the OLE studies.
The most common treatment-related adverse finding was elevation of cerebrospinal fluid (CSF) protein levels. These elevations were observed in 14% of patients in the Phase 1/2a trial and 45% in the OLE study. Higher CSF protein levels exceeding 50 mg/dL were reported in a larger proportion of patients, particularly in the OLE phase; however, investigators noted that these laboratory abnormalities were not associated with clinical symptoms in the vast majority of cases. Only one patient discontinued treatment due to elevated CSF protein levels.
Serious adverse events were reported in 22% of Phase 1/2a patients and 29% of OLE patients, though nearly all were deemed unrelated to zorevunersen. Three deaths have occurred across both studies—two from sudden unexpected death in epilepsy (SUDEP) and one from malnutrition—all of which were assessed as unrelated to treatment.
At AES, researchers delivered a series of oral and poster presentations detailing these findings. An oral session led by Dr. Perry focused on long-term outcomes from the open-label extension studies, reinforcing the durability of seizure reductions and continued functional improvements. Additional poster sessions covered quality-of-life gains, global clinical status improvements, longitudinal EEG abnormalities across development in Dravet syndrome, and electrophysiological changes following zorevunersen treatment.
Together, these presentations painted a consistent picture across clinical, functional, and biological domains: zorevunersen is demonstrating multi-dimensional benefits that extend well beyond seizure control alone. This breadth of impact is particularly relevant in Dravet syndrome, where treatment goals increasingly emphasize developmental preservation, cognitive function, behavioral stability, and overall family well-being.
The companies emphasized that while these open-label and comparative analyses are highly encouraging, the randomized, sham-controlled Phase 3 EMPEROR trial remains the definitive test of zorevunersen’s clinical benefit. EMPEROR is currently enrolling patients globally and is designed to confirm the therapy’s efficacy on seizure frequency, cognitive outcomes, and safety in a controlled setting.
If successful, zorevunersen could become the first disease-modifying therapy approved for Dravet syndrome—an achievement that would represent a landmark shift in how this condition is managed. Existing therapies primarily aim to suppress seizures without addressing the underlying pathogenic mechanism, leaving patients at continued risk of developmental decline.
For families affected by Dravet syndrome, the promise of a therapy that could meaningfully alter the disease trajectory offers renewed hope. For clinicians and researchers, the data presented at AES mark an important step forward in translating genetic and molecular insights into tangible clinical benefit.
As further results from the EMPEROR trial emerge, the global epilepsy community will be closely watching whether zorevunersen can fulfill its early promise and usher in a new era of precision, disease-modifying treatment for one of the most challenging forms of childhood epilepsy.
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).
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
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.
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