Zorevunersen

A disease-modifying RNA therapy that targets the genetic root cause of Dravet syndrome by increasing production of the Nav1.1 protein that patients lack. Unlike current symptom-suppressing drugs, zorevunersen addresses the underlying SCN1A deficiency. Received FDA Breakthrough Therapy Designation.

In Dravet syndrome, one copy of the SCN1A gene is broken, meaning your body makes only half the Nav1.1 protein it needs. Zorevunersen is an RNA therapy injected into the spinal fluid that tricks the working gene copy into producing more Nav1.1 protein. It does this by blocking a 'poison exon' in the RNA instructions that normally limits protein production, essentially unlocking more output from the good gene copy.

In the Phase 1/2a and open-label extension studies, Stoke reported in September 2026 that about 94% of patients had raised protein in the spinal fluid (CSF) on lab tests. No serious or severe symptoms were linked to these rises, and there were no reports of hydrocephalus^[1]. The spinal injection itself carries the usual risks of a lumbar puncture.

Given as an intrathecal injection (into the spinal fluid via lumbar puncture) at a medical center. In EMPEROR, patients receive 70 mg on Day 1 and at Week 8, then 45 mg at Weeks 24 and 40, which works out to maintenance doses about every 4 months.

Zorevunersen is currently in phase 3 clinical trials for Dravet Syndrome. It has not yet received FDA approval.

Current Dravet therapies (stiripentol, cannabidiol, fenfluramine) reduce seizure frequency by modulating brain activity but do not address the underlying genetic cause. Zorevunersen is a disease-modifying therapy that targets the root cause by increasing production of the Nav1.1 sodium channel protein that Dravet patients lack due to SCN1A mutations. By restoring protein levels rather than just suppressing symptoms, it has the potential to improve both seizures and the developmental problems associated with Dravet syndrome.

A poison exon is a naturally occurring segment of genetic code that, when included in the RNA instructions, causes the resulting protein to be degraded rather than produced. The SCN1A gene contains such a poison exon that normally limits Nav1.1 production. Zorevunersen is an antisense oligonucleotide that blocks this poison exon, allowing the working copy of the SCN1A gene to produce more functional Nav1.1 protein than it normally would.

Yes. Unlike gene therapy approaches that aim for a one-time correction, zorevunersen requires ongoing intrathecal injections to maintain its effect. After loading doses at Day 1 and Week 8, maintenance doses are given every 4 months. The effect is not permanent because the antisense oligonucleotide is gradually cleared from the body over time.

EMPEROR (NCT06872125) is the global Phase 3 trial of zorevunersen in children aged 2 to under 18 with Dravet syndrome caused by SCN1A variants that are not gain-of-function. It is randomized, double-blind and sham-controlled. The main goal is the change in major motor seizure frequency at Week 28, with longer-term effects and cognition measured at Week 52. Its main analysis group of 162 patients finished enrolling in June 2026, and data are expected in the third quarter of 2027.

In the earlier Phase 1/2a studies, patients receiving zorevunersen showed improvements in cognition and behavior in addition to seizure reduction. These studies were open-label, so the Phase 3 EMPEROR trial, which measures cognition and behavior at Week 52, will give a clearer answer.