Zorevunersen tied to long-term benefits in Dravet syndrome
Four-year data show sustained seizure, cognition improvements
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Zorevunersen, Stoke Therapeutics’ investigational therapy for Dravet syndrome, remained generally well tolerated and was associated with sustained seizure reductions and cognitive and behavioral improvements for up to four years.
The findings come from two long-term extension studies — SWALLOWTAIL (NCT04740476) and LONGWING (ISRCTN12811235) — that followed participants who previously took part in two Phase 1/2a trials.
Stoke also announced that enrollment of about 150 patients in the U.S., U.K., and Japan portion of the global Phase 3 EMPEROR trial (NCT06872125) is expected to be completed in June. Data from the study are expected in mid-2027 and, if positive, are expected to support the company’s U.S. regulatory submission.
Zorevunersen aims to raise NaV1.1 levels
“These new 4-year … data suggest that zorevunersen may change the course of Dravet syndrome by providing children with durable reductions in seizures and the possibility of a more neurotypical development path,” Ian F. Smith, Stoke’s CEO and director, said in a company press release.
“As we continue to see this study through to completion, our focus turns increasingly to commercial preparedness and bringing zorevunersen to patients,” Smith added. “All of this is supported by our strong financial position taking us through to a potential U.S. launch in early 2028.”
Dravet syndrome is mainly caused by mutations in the SCN1A gene, which result in reduced levels of functional NaV1.1, a sodium channel that helps control when nerve cells fire. This is thought to enable excessive nerve cell firing, ultimately leading to seizures and other Dravet symptoms.
Zorevunersen, previously known as STK-001, contains a small strand of genetic material, called an antisense oligonucleotide, designed to increase functional NaV1.1 production from the unaffected, or working, copy of the SCN1A gene. The therapy is administered into the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord, through a lumbar puncture.
The treatment’s safety, how it moved through the body, and its exposure in the CSF were evaluated in two parallel, open-label Phase 1/2a trials — MONARCH (NCT04442295) and ADMIRAL (ISRCTN99651026) — that collectively enrolled 81 children with Dravet, ages 2 to 18 years. In both trials, participants received zorevunersen as a single or multiple dose, in addition to their standard anti-seizure medications.
Most patients entered extension studies
After the main trials, most participants — 93%, or 75 of 81 — continued treatment in the open-label extension (OLE) studies SWALLOWTAIL and LONGWING. As of the four-year data cutoff, 77%, or 58 of 75, remained in the studies.
Earlier results from the extension studies showed that children treated with zorevunersen maintained long-lasting seizure reductions and experienced improvements in cognition, behavior, socialization, and clinical condition. These beneficial effects were sustained through three years of treatment in the OLE trials, and those findings were recently published.
The new four-year longitudinal data showed that patients continued to experience durable reductions in seizures and had statistically significant improvements in cognition and behavior at years 1, 2, 3, and 4 compared with the start of the OLE studies. Additionally, the treatment remained generally well tolerated, with some patients receiving treatment for more than five years.
Elevated CSF protein lab values occurred in about 94% of participants, and 59% were classified as treatment-emergent adverse events. Stoke said these elevations were not associated with serious or severe clinical symptoms, and there were no reports of hydrocephalus, a buildup of fluid in the brain.
“Together with the Phase 1/2a results, the ongoing extension studies offer 5 years of clinical data, providing a unique opportunity to understand the long-term benefits and safety of zorevunersen,” Smith said.
