Stoke Therapeutics and Biogen Announce Publication of Two-Year Natural History Data Demonstrating the Severity of Dravet Syndrome, Including Frequent Seizures and Significant Cognitive and Behavioral Impairments
– Despite treatment with standard-of-care anti-seizure medicines, children with Dravet syndrome experienced high seizure burden and plateaued in neurodevelopment, resulting in a widening gap relative to children with typical development –
– Findings underscore the urgent need for new medicines that target the underlying genetic cause of Dravet syndrome to improve long-term outcomes –
Stoke Therapeutics, Inc. (NASDAQ:STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body's potential with RNA medicine, and Biogen Inc. (NASDAQ:BIIB) today announced the publication of final data from the BUTTERFLY study, a prospective, two-year natural history study in people with Dravet syndrome. Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by recurrent seizures and significant cognitive and behavioral impairments. There are currently no approved disease-modifying medicines to treat Dravet syndrome.
The BUTTERFLY study evaluated the impact of Dravet syndrome on adaptive functioning and neurodevelopment over two years in children and adolescents ages 2 to 18 years old. Major motor seizure frequency was evaluated as a secondary outcome measure. In the study, patients were treated with standard-of-care, including anti-seizure medicines (ASMs). Highlights from the research, published November 14, 2025, in Neurology®, 1 the medical journal of the American Academy of Neurology, include:
- Regardless of the age at which patients with Dravet syndrome entered the study, neurodevelopment plateaued at the developmental age of approximately two years old. This created a gap that widened over time versus what would be expected for children with typical development.
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Results showed that over the course of the two-year study, patients experienced minimal changes in cognition and behavior, including communication, motor skills and personal skills, compared to typical neurodevelopment expected for children of the same age.
- Assessments of cognition and behavior used in BUTTERFLY were pre-determined endpoints that were incorporated into this natural history study to support use in future clinical studies of Dravet syndrome. They included the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3); Bayley Scales of Infant Development, Third Edition (BSID-III); and Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). These assessments, as well as other outcome measures used in BUTTERFLY, are consistent with the primary and secondary endpoints of the pivotal, global Phase 3 EMPEROR study evaluating zorevunersen as a potential disease-modifying medicine for the treatment of Dravet syndrome.
- Major motor seizure frequency increased by 10.6 percent over two years (average of 14.3 seizures/28 days at baseline; p=0.63; n=23).
"These natural history data confirm that the life-altering effects of Dravet syndrome extend well beyond seizures, resulting in significant deficits in patients' functioning and development despite treatment with the best available medicines," said Joseph Sullivan, M.D., FAES, lead author of the Neurology publication and Professor of Neurology and Pediatrics at the University of California San Francisco. "The findings make clear that as children with Dravet syndrome grow up, they experience a widening gap in their cognitive and behavioral development compared to a neurotypical child of the same age. By giving us a baseline characterization of what current treatments can do for patients, these data become increasingly important in helping us understand how potential disease-modifying medicines might change the trajectory of Dravet syndrome. I'd like to extend my deep appreciation to the families who participated in BUTTERFLY and made significant sacrifices to help us more fully comprehend the debilitating effects of this disease."
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. More than 90 percent of patients continue to experience seizures despite treatment with the best available anti-seizure medicines. 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 infections.2 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.3 There are no approved disease-modifying therapies for people living with Dravet syndrome.
About the BUTTERFLY Study
The BUTTERFLY study was a multicenter, longitudinal, prospective, observational study of children and adolescents ages 2 to 18 who have been diagnosed with Dravet syndrome as a result of an SCN1A gene mutation. The study was designed to evaluate neurodevelopmental status and change from baseline to 24 months. Secondary and exploratory endpoints in the study evaluated changes in other disease measures, including seizures and additional measures of cognition, behavior and overall functioning. No investigational medications or other treatments were provided. Participants continued to receive optimized standard of care, including anti-seizure medications, and were observed for up to two years. The study was conducted at approximately 20 sites in the U.S.
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/.
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.
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References:
1 Sullivan J, Wirrell E, Knupp K. et al. Natural history of children and adolescents with Dravet syndrome: a 24-month follow-up. Neurology. 2025;105:e214388
2 Symonds, J. et al. Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants. Brain. 2021;144(9):2879-2891.
3Based 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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