Bedford, Massachusetts and Cambridge, Massachusetts, USA, September 3, 2026
Biogen Inc. and Stoke Therapeutics have presented new long-term clinical data supporting the potential of zorevunersen, an investigational RNA-based therapy being developed for Dravet syndrome, a severe developmental and epileptic encephalopathy. The findings, presented at the 16th European Epilepsy Congress (EEC) in Athens, Greece, include up to four years of open-label extension data showing durable seizure reductions, continued improvements in cognition and behavior, and quality-of-life benefits. The companies also reported reductions in the most severe seizure types associated with increased risk of sudden unexpected death in epilepsy (SUDEP). Zorevunersen remains investigational, and its safety and efficacy have not been evaluated by any regulatory authority.
Long-Term Data Show Durable Seizure Reduction
The latest evidence comes from patients who participated in two Phase 1/2a studies and subsequently entered ongoing open-label extension (OLE) studies. These programs have generated more than five years of clinical experience with zorevunersen in people with Dravet syndrome. Of 81 eligible patients from the Phase 1/2a studies, 93% continued into the OLE studies, with 77% remaining in the studies at the four-year data cutoff. Patients receiving zorevunersen alongside standard anti-seizure medicines continued to demonstrate reductions in seizures, while statistically significant improvements in cognition and behavior were observed at one, two, three and four years compared with the OLE baseline. An exploratory analysis also examined the most severe seizure types, including generalized tonic-clonic (GTC) and focal-to-bilateral tonic-clonic seizures. These seizure categories are associated with substantial morbidity and mortality in epilepsy, making the reported reductions clinically important for further evaluation. The companies said substantial reductions in these severe seizures were observed through three years of OLE treatment compared with the Phase 1/2a baseline. The findings add to the clinical evidence being generated around a potential therapy designed to address an underlying genetic mechanism rather than solely controlling seizure symptoms.
Zorevunersen Targets the Underlying SCN1A Mechanism
Zorevunersen is an investigational antisense oligonucleotide designed to increase functional NaV1.1 protein production from the unaffected copy of the SCN1A gene. Most cases of Dravet syndrome are associated with mutations in one copy of SCN1A, resulting in insufficient NaV1.1 protein in neuronal cells. The therapy uses Stoke Therapeutics’ TANGO RNA medicine approach to selectively increase production of the naturally occurring protein. The long-term findings also included a quality-of-life analysis showing substantial improvements through 28 months compared with the Phase 1/2a baseline, based on the EuroQol Visual Analog Scale. Safety and tolerability remain important considerations because treatment is administered through intrathecal delivery, and patients in the OLE studies have received treatment for more than five years. As of July 31, 2026, more than 930 doses had been administered. Elevated cerebrospinal fluid protein levels were reported in approximately 94% of patients, although the companies stated that these elevations had not been associated with serious or severe clinical manifestations and no cases of hydrocephalus had been reported.
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Phase 3 EMPEROR Data Expected in 2027
The development program is advancing into the pivotal Phase 3 EMPEROR study, a global, randomized, double-blind and sham-controlled trial evaluating zorevunersen in children aged 2 to under 18 years with Dravet syndrome and a confirmed SCN1A variant not associated with gain-of-function. Enrollment has been completed in the United States, United Kingdom and Japan, while European enrollment also concluded in August 2026. Enrollment is continuing in China. The primary endpoint of EMPEROR is the percentage change from baseline in major motor seizure frequency at Week 28, while key secondary measures include durability of seizure reduction and changes in cognition and behavior. A Phase 3 data readout is anticipated in the third quarter of 2027, supporting the companies’ planned rolling New Drug Application (NDA) submission to the U.S. FDA in the second half of 2027. Until those results are available, zorevunersen remains an investigational therapy.
Source: Biogen press release
