Zorevunersen for Dravet syndrome
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Zorevunersen (STK-001) is an investigational therapy being developed by Stoke Therapeutics for the treatment of Dravet syndrome. It is administered via intrathecal injections, which are given into the spinal canal.
Seizures in Dravet syndrome typically arise from mutations in the SCN1A gene, which result in too little functional NaV1.1, a sodium channel that helps control when nerve cells fire. Too little NaV1.1 in certain nerve cells can lead to the excessive brain activity that causes seizures.
People with Dravet generally have one healthy copy of SCN1A that works as it should, and one mutated version that doesn’t.
Zorevunersen aims to reduce seizures in Dravet by increasing the activity of the healthy SCN1A copy, helping compensate for the faulty gene and allowing more functional NaV1.1 to be produced. The therapy contains a small strand of genetic material called an antisense oligonucleotide. It is designed to bind to RNA made from the healthy SCN1A gene copy, helping cells produce more functional NaV1.1 protein.
The medication is currently being tested in a Phase 3 trial, with results expected in 2027. The data may support a regulatory application seeking zorevunersen’s approval for Dravet syndrome.
Therapy snapshot
| Treatment name | Zorevunersen |
| Administration | Intrathecal injection |
| Clinical testing | Currently in Phase 3 testing |
How will zorevunersen be administered in Dravet syndrome?
Zorevunersen is administered via intrathecal injections. In an ongoing Phase 3 trial involving children with Dravet syndrome, participants assigned to zorevunersen receive two initial 70 mg loading doses about two months apart, followed by 45 mg maintenance doses about once every three to four months.
Zorevunersen in Dravet syndrome clinical trials
The Phase 3 EMPEROR trial (NCT06872125) is evaluating the safety and efficacy of zorevunersen in children with Dravet syndrome, ages 2-17, who are still having motor seizures despite prior treatment with at least two antiseizure medications and are currently taking at least one antiseizure medication.
In the first treatment period, participants will receive zorevunersen or undergo sham procedures. In the second treatment period, participants who initially received zorevunersen will continue receiving it, while those who initially underwent sham procedures will start zorevunersen. The main goal is to evaluate changes in major motor seizure frequency; behavior, cognition, clinical status, safety, and quality of life will also be measured. After the study, participants may continue treatment in an open-label extension study.
Zorevunersen has been previously tested in two Phase 1/2a clinical trials — MONARCH (NCT04442295) and ADMIRAL (ISRCTN99651026) — and their ongoing open-label extension studies — SWALLOWTAIL (NCT04740476) and LONGWING (ISRCTN12811235).
People with Dravet, ages 2 to 18, who were receiving standard medications, received zorevunersen injections at varying dose levels. Published data from the Phase 1/2a trials and their extension studies suggested that zorevunersen was associated with:
- substantial reductions in motor seizure frequency that were sustained through three years of treatment
- improvements in communication, motor skills, socialization, daily living, and quality of life
Zorevunersen side effects
In Phase 1/2a studies and their extensions, the most common side effect considered to be treatment-related was elevated protein levels in the cerebrospinal fluid, which surrounds the brain and spinal cord. No related clinical symptoms were observed.
Serious adverse events were reported, but all were deemed unrelated to zorevunersen except in one participant.
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