Stoke Therapeutics and Biogen have reported long-term zorevunersen data showing sustained seizure reductions and continuing improvements in cognition and behavior among patients with Dravet syndrome treated on top of standard antiseizure medicines. The new analyses draw on more than five years of clinical experience across Phase 1/2a and open-label extension studies, with 93% of eligible participants entering the extensions and 77% of those participants remaining in the studies at the four-year data cutoff. The companies plan to present the findings at the 16th European Epilepsy Congress while the pivotal Phase 3 EMPEROR study progresses toward a third-quarter 2027 readout.
The significance extends beyond reducing seizure counts because Dravet syndrome is a severe developmental and epileptic encephalopathy that affects cognition, communication, behavior, movement and independence. Stoke and Biogen reported statistically significant improvements in cognition and behavior at one, two, three and four years compared with open-label extension baseline, along with improvements in quality of life through 28 months. These analyses remain uncontrolled extension data, meaning the pivotal randomized Phase 3 study will ultimately provide the more rigorous test of whether zorevunersen produces disease-modifying benefit.
What happened to seizures during long-term zorevunersen treatment?
Patients treated with zorevunersen continued to show durable reductions in seizures while remaining on standard antiseizure medicines. A new exploratory analysis focused specifically on generalized tonic-clonic and focal-to-bilateral tonic-clonic seizures, among the most severe seizure types and those strongly associated with morbidity and sudden unexpected death in epilepsy. Stoke and Biogen reported substantial reductions in these severe seizures through three years compared with baseline before zorevunersen treatment.
That endpoint has particular relevance in Dravet syndrome because SUDEP is a major cause of premature mortality. The companies estimate that as many as 20% of children and adolescents with Dravet syndrome die before adulthood from SUDEP, prolonged seizures, seizure-associated accidents or infections. The current analysis does not establish that zorevunersen reduces mortality, but a durable reduction in severe convulsive seizures provides a biologically and clinically important signal that the Phase 3 program will need to place into a controlled framework.
Why could cognition and behavior be more important than seizure reduction alone?
Existing antiseizure medicines can reduce seizure frequency but do not directly correct the genetic defect responsible for most Dravet syndrome. Children often continue experiencing developmental delays, language impairment, movement difficulties, sleep abnormalities and behavioral problems even when seizures become better controlled. A therapy capable of improving neurological development in addition to reducing seizures would therefore address a substantially broader portion of the disease burden.
Stoke’s therapeutic hypothesis is that increasing functional NaV1.1 protein can restore some of the biology disrupted by SCN1A loss-of-function mutations. Continued improvements in cognition and behavior through four years are therefore central to the disease-modification argument. Because these observations come from open-label extensions without a long-term randomized comparator, EMPEROR will be critical in separating drug effect from developmental variation, changes in background treatment and other factors that can influence long-term outcomes.
How does zorevunersen address the SCN1A mutation behind Dravet syndrome?
Most Dravet syndrome cases arise when one copy of the SCN1A gene does not produce enough functional NaV1.1 sodium-channel protein. Zorevunersen is an antisense oligonucleotide designed to increase expression of NaV1.1 from the unaffected copy of the gene rather than attempting to edit the mutation itself. The goal is to restore protein output toward a level sufficient to improve neuronal function.
This is fundamentally different from another anticonvulsant mechanism layered on top of an already complicated drug regimen. If the approach succeeds, the medicine could potentially alter several manifestations of disease because the treatment acts upstream at the level of protein expression. Zorevunersen has received FDA Breakthrough Therapy, Rare Pediatric Disease and Orphan Drug designations, but it remains investigational and has not yet demonstrated the controlled Phase 3 evidence needed for approval.
What has emerged from more than 930 administered zorevunersen doses?
Stoke and Biogen reported that more than 930 doses had been administered by July 31, 2026, with some patients treated for more than five years. The medicine continues to be described as generally well tolerated, but cerebrospinal-fluid protein elevations have become one of the clearest laboratory findings. Approximately 94% of patients developed elevated CSF protein values, with 59% classified as treatment-emergent adverse events.
The companies reported no serious or severe clinical manifestations associated with those elevations and no cases of hydrocephalus. That is reassuring but does not make the laboratory finding irrelevant, particularly for a therapy intended to continue over years. Long-term safety surveillance and Phase 3 experience will need to establish whether persistent CSF protein elevations remain clinically benign across a larger population and longer cumulative exposure.
How is the Phase 3 EMPEROR trial designed to provide a stronger answer?
The global pivotal EMPEROR study has completed enrollment in its planned primary-analysis population of 162 patients in the United States, United Kingdom and Japan. Patients are being evaluated against sham administration through lumbar puncture, creating a controlled comparison designed to separate the pharmacological effect of zorevunersen from procedural and expectation effects. Another 34 participants have been enrolled in Europe.
Phase 3 data are expected in the third quarter of 2027 and are intended to complete a rolling U.S. New Drug Application planned for the second half of that year. That timeline means the long-term extension data provide supportive evidence rather than the final regulatory answer. A successful pivotal study showing both seizure and neurodevelopmental benefit could make zorevunersen one of the most important genetically targeted medicines developed for developmental epilepsy.
What should the Dravet community watch between now and the Phase 3 readout?
The key issue is whether the magnitude and breadth of long-term improvement remain visible under randomized conditions. Open-label extension data can be highly valuable for durability and safety, especially in rare pediatric diseases, but they are vulnerable to selection because patients benefiting from treatment may be more likely to remain enrolled. EMPEROR therefore needs to show that zorevunersen produces meaningful benefit compared with a concurrently treated control population.
The other question is how regulators will weigh multiple dimensions of Dravet syndrome. Seizure frequency is clinically important and measurable, but families often describe communication, cognition, behavior and independence as equally consequential. If the Phase 3 dataset demonstrates benefits across both seizure and developmental domains, zorevunersen could help redefine what a successful Dravet therapy is expected to achieve.
