Stoke Therapeutics and Biogen have released new long-term data on their investigational drug zorevunersen, which is being developed for the treatment of Dravet syndrome, a rare and difficult-to-treat form of epilepsy. The findings were presented at the 2025 annual meeting of the American Epilepsy Society.
According to a news release issued by the companies, a propensity score-weighted analysis was used to compare patients treated with zorevunersen across its clinical program to natural history controls. This approach was intended to balance baseline differences between groups in order to “mimic randomization.”
The results indicated that patients receiving zorevunersen experienced a “statistically significant” reduction in major motor seizure frequency at six months compared to external controls, although specific data figures were not included in the announcement. Analysts at Jefferies noted in a separate commentary that among five patients who received two 70-mg loading doses of zorevunersen, there was an 82% decrease in major motor seizures over six months. In comparison, natural history comparators had a 20% reduction during the same period.
The data also showed that this benefit persisted through 24 months: those on zorevunersen saw a 76% drop in seizures versus 25% among external comparators. Additionally, Stoke and Biogen reported improvements across five cognitive and behavioral measures following treatment with zorevunersen. They stated that “several” changes reached statistical significance but did not provide detailed numbers.
“By ensuring both groups have similar baselines, [the companies] can present efficacy that more closely mimics potential Phase III outcomes,” according to Jefferies. In this context, these new Dravet data are “partially de-risking” for zorevunersen’s ongoing Phase III EMPEROR trial.
Dravet syndrome affects about one in every 15,700 people. It begins in infancy and is marked by frequent and prolonged seizures as well as developmental delays and movement difficulties. Most cases are linked to mutations in the SCN1A gene. Zorevunersen targets SCN1A mRNA to prevent certain mutations from producing faulty proteins—a mechanism Stoke says addresses the underlying cause of Dravet syndrome.
Enrollment for the Phase III EMPEROR study of zorevunersen is ongoing. Stoke recently announced plans to meet with the FDA before year end regarding potential expedited regulatory pathways for the drug.
