Stoke and Biogen present 4-year zorevunersen data at EEC

Stoke Therapeutics and Biogen have presented long-term clinical data for zorevunersen, their investigational antisense oligonucleotide (ASO) for Dravet syndrome, at the 16th European Epilepsy Congress in Athens. The data, drawn from Phase 1/2a open-label extension (OLE) studies covering up to five years of treatment, showed sustained reductions in seizure frequency alongside continuing improvements in cognition, behaviour, and quality of life.

Dravet syndrome is a severe developmental and epileptic encephalopathy caused in most cases by mutations in the SCN1A gene, which leads to insufficient production of the NaV1.1 sodium-channel protein in brain cells. Even with the best available anti-seizure medicines, nearly 57% of patients do not achieve a 50% or greater reduction in seizure frequency, and up to 20% of children and adolescents with the condition die before adulthood. There are currently no approved disease-modifying therapies for the disorder.

What the data showed

At the four-year OLE data cutoff, 77% of the 75 eligible patients who entered the extensions remained in the studies. Statistically significant improvements in cognition and behaviour, measured by the Vineland Adaptive Behavior Scales (Vineland-3), were recorded at one, two, three, and four years compared to OLE baseline. A new exploratory sub-analysis reported substantial reductions in generalised tonic-clonic (GTC) and focal-to-bilateral tonic-clonic seizures, the most severe categories and the type most strongly correlated with sudden unexpected death in epilepsy (SUDEP). A separate sub-analysis using the EuroQol Visual Analog Scale showed meaningful quality-of-life gains through 28 months. Zorevunersen is administered intrathecally every four months; more than 930 doses have been given to date, and some patients have been on treatment for over five years.

Helen Cross, Professor and Director of the UCL Great Ormond Street Institute of Child Health, said the cognition and behaviour improvements suggested zorevunersen had "the potential to narrow the developmental gap between these children and their neurotypical peers, helping them gain more independence."

On safety, elevated cerebrospinal fluid protein values were observed in approximately 94% of patients, of which 59% were classified as treatment-emergent adverse events. The companies said no serious or severe clinical manifestations were associated with these elevations, and no cases of hydrocephalus were reported.

Regulatory path and competitive landscape

The companies are now running the global, double-blind Phase 3 EMPEROR study (NCT06872125) in children aged 2 to under 18. Enrolment in the primary analysis population of 162 patients across the US, UK, and Japan completed in June 2026; European enrolment of 34 participants closed in August. Enrolment in China is ongoing. A Phase 3 data readout is anticipated in Q3 2027 to support completion of a rolling New Drug Application to the FDA, targeted for the second half of 2027. Zorevunersen already holds FDA Breakthrough Therapy Designation, Rare Pediatric Disease designation, and orphan drug status from both the FDA and EMA.

The Dravet therapeutic landscape has become increasingly competitive in recent years. Fenfluramine (Fintepla, UCB) and cannabidiol (Epidyolex, Jazz Pharmaceuticals) have both gained approval as adjunctive seizure-reduction therapies but do not address the underlying SCN1A haploinsufficiency. No disease-modifying agent has yet reached approval. Stoke's TANGO platform, which upregulates output from the unaffected wild-type allele, is differentiated mechanistically from both small-molecule and gene-replacement approaches being explored by other groups. A successful Phase 3 readout and NDA would position zorevunersen as the first approved therapy targeting the root genetic cause of the disease, potentially qualifying for an FDA Rare Pediatric Disease priority review voucher, which carries significant commercial value in its own right.

Investors will focus on whether the Phase 3 primary endpoint, percent change from baseline in major motor seizure frequency at week 28, confirms the efficacy signal seen in the earlier open-label work, and whether the safety profile in the controlled setting is consistent with OLE experience.