Four-year open-label extension data for zorevunersen, the antisense oligonucleotide being developed by Massachusetts-based Stoke Therapeutics (Nasdaq: STOK) and Biogen (Nasdaq: BIIB) for Dravet syndrome, show that seizure reductions and neurodevelopmental gains observed in earlier studies persist through at least four years of treatment. The disclosure adds to a clinical dataset that the companies say supports a disease-modifying profile ahead of a pivotal Phase III readout expected in Q3 2027. The data were presented at the 16th European Epilepsy Congress in Athens.
Dravet syndrome is caused in most cases by loss-of-function mutations in one copy of the SCN1A gene, reducing Nav1.1 sodium channel expression in neurons. Zorevunersen redirects non-productive splicing of SCN1A pre-mRNA, increasing Nav1.1 protein output from the intact allele. The three drugs currently approved specifically for Dravet syndrome — Jazz Pharmaceuticals' Epidiolex (cannabidiol), Biocodex's Diacomit (stiripentol), and UCB's Fintepla (fenfluramine) — are all oral symptomatic agents that do not address the underlying genetic deficit. No approved disease-modifying therapy exists for the condition.
Of the 81 patients enrolled across two Phase I/IIa open-label studies, 93% (75/81) of eligible patients entered open-label extensions (OLEs). At the four-year data cutoff, 77% (58/75) remained on treatment. Statistically significant improvements in cognition and behavior, measured by the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), were demonstrated at one, two, three, and four years compared to OLE baseline. A new exploratory sub-analysis reported substantial reductions in generalized tonic-clonic and focal-to-bilateral tonic-clonic seizures — the seizure types most strongly correlated with sudden unexpected death in epilepsy (SUDEP) — through three years of the OLEs versus Phase I/IIa baseline. A separate sub-analysis showed substantial improvements in quality of life, measured by the EuroQol Visual Analog Scale, through 28 months. More than 930 doses have been administered as of July 31, 2026, with some patients treated for more than five years. Elevated cerebrospinal fluid protein values occurred in approximately 94% of patients, of which 59% were classified as treatment-emergent adverse events; no serious or severe clinical manifestations were associated with these elevations, and no cases of hydrocephalus were reported.
These data extend a clinical narrative that has been building since Phase I/IIa results were published in the New England Journal of Medicine in March 2026 and three-year OLE findings were presented at the 36th International Epilepsy Congress in September 2025. The FDA granted zorevunersen Breakthrough Therapy Designation in December 2024, and the agency has also granted orphan drug and rare pediatric disease designations. China's Center for Drug Evaluation has separately granted Breakthrough Therapy Designation.