Stoke Therapeutics and Biogen present long-term zorevunersen data for Dravet syndrome

At the 16th European Epilepsy Congress (EEC) in Athens, Greece, Stoke Therapeutics and Biogen presented long-term clinical data that support the potential of zorevunersen as a disease-modifying treatment for Dravet syndrome. The findings, derived from over four years of treatment, have significant implications for the management of this severe developmental and epileptic encephalopathy (DEE).

The data, presented by Stoke Therapeutics’ Chief Medical Officer, Barry Ticho, and Biogen’s Head of the Rare Neurology Development Unit, Stephanie Fradette, showed substantial and durable reductions in seizures among patients treated with zorevunersen in combination with standard anti-seizure medications. Furthermore, the drug demonstrated ongoing improvements in cognition and behavior, with reductions in the most severe seizure types, which are the leading risk factor for sudden unexpected death in epilepsy (SUDEP).

"These data are particularly meaningful because they show significant reductions in the severe seizures most strongly correlated with SUDEP, and demonstrate ongoing improvements in the neurodevelopmental aspects of the disease," Ticho stated.

Additionally, quality of life improved substantially over 28 months, as measured by the EuroQol Visual Analog Scale (EQ-VAS). This scale, which ranges from 0 to 100, offers insight into the real-world impact of zorevunersen on patients and their families.

Dr. Helen Cross, a leading expert in childhood epilepsy from the University of College London, highlighted the potential of zorevunersen in closing the developmental gap between children with Dravet syndrome and their neurotypical peers. "Seizures are just the tip of the iceberg in Dravet syndrome. The continuing improvements in cognition and behavior are encouraging and suggest that zorevunersen could offer a significant breakthrough in managing this condition."

The global, pivotal Phase 3 EMPEROR study, currently enrolling patients, is expected to provide additional insights. It aims to evaluate the efficacy and safety of zorevunersen compared to a sham treatment via lumbar puncture. Enrollment has completed in the primary analysis population, which consists of 162 patients from the U.S., U.K., and Japan. A data readout is anticipated in the third quarter of 2027 to support the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of that year.

Zorevunersen, an investigational antisense oligonucleotide, is designed to increase functional NaV1.1 protein production in brain cells, addressing the genetic root of Dravet syndrome. The drug has shown promising results in reducing seizure frequency and improving neurodevelopment, cognition, and behavior. According to Ticho, the safety data from the ongoing open-label extension studies demonstrate that zorevunersen continues to be well tolerated, with some patients treated for more than five years.

"Up to 20% of children and adolescents with Dravet syndrome die before reaching adulthood, and SUDEP is the primary cause," Fradette noted. "These data are crucial because they show substantial reductions in the severe seizures most strongly correlated with SUDEP and continue to demonstrate improvements in the debilitating neurodevelopmental aspects of the disease."

The findings at EEC underscore the potential of zorevunersen to offer a transformative treatment for Dravet syndrome, potentially altering the course of the disease and improving the quality of life for patients and their families.