Zorevunersen Cuts Dravet Seizures by Up to 91% in 81-Child Trial

Seizure frequency in children with Dravet syndrome fell by as much as 91 percent during an international trial of zorevunersen, an investigational drug that increases production of a key sodium channel protein from the healthy copy of the SCN1A gene, in findings reported March 4, 2026 in The New England Journal of Medicine by University College London researchers.

For eight-year-old Freddie in Huddersfield, the trial's headline reduction arrived as a quieter bedroom. The same trend showed up at home after he joined the 2021 trial at Sheffield Children's NHS Foundation Trust: his nightly seizure count dropped from more than a dozen to one or two brief events every three to five days.

His mother Lauren said: "The trial has completely changed our lives. We now have a life we didn't ever think was possible and most importantly it's a life that Freddie can enjoy."

The headline result draws on 81 patients aged two to 18 at sites in the United Kingdom and the United States. Among children who received 70 mg doses during the first stage of the trial, seizure frequency dropped between 59 percent and 91 percent over the first 20 months of follow-up. Compared with pre-treatment baselines, the reduction held across the cohort. Seventy-five of 81 children continued into the extension phase, where maintenance infusions were given every four months.

What does Dravet syndrome mean for the neurophysiology clinic?

Dravet syndrome is a developmental and epileptic encephalopathy, meaning refractory seizures coexist with cognitive and behavioral regression. Most cases trace to a loss-of-function variant in one copy of SCN1A, which encodes the Nav1.1 sodium channel subunit (a pore-forming protein that lets neurons fire). Existing antiseizure medications reduce convulsive events in some patients; none targets the underlying genetic deficit.

How does zorevunersen act on the genetic cause?

Stoke Therapeutics, with Biogen, designed zorevunersen to increase production of the Nav1.1 protein from the patient's healthy SCN1A copy rather than replace the faulty allele. Investigators delivered doses of up to 70 mg by lumbar puncture (injection into the lower spinal canal).

What did the trial measure?

The initial open-label phase (clinicians and families knew the assigned treatment) enrolled patients who averaged 17 seizures per month at baseline. Investigators tracked safety and tolerability as primary endpoints, with seizure frequency, cognition, behavior, and quality of life as secondary measures. Most adverse events were mild.

Lead investigator Professor Helen Cross, Director of the UCL Institute of Child Health and Honorary Consultant in Paediatric Neurology at Great Ormond Street Hospital, said: "I regularly see patients with hard-to-treat genetic epilepsies with impacts that go beyond seizures and it's heart-breaking when treatment options are limited. This new treatment could help children with Dravet syndrome lead much healthier and happier lives."

Cross added: "Overall, our findings showed that zorevunersen is safe to use and well tolerated by most patients and supports further evaluation in the ongoing Phase Three study."

Where were UK patients treated?

Nineteen of the 81 children received care at four British centers:

• Great Ormond Street Hospital
• Sheffield Children's Hospital
• Evelina London Children's Hospital
• The Royal Hospital for Children in Glasgow

At GOSH, dosing took place at the National Institute for Health and Care Research Clinical Research Facility, a unit built for pediatric experimental medicine.

Galia Wilson, Chair of Trustees at Dravet Syndrome UK, said: "We regularly see the devastating impact that this condition has on the lives of families. That's why we're so thrilled about these latest results from the initial zorevunersen clinical trials."

Wilson added: "We're now looking forward to the Phase Three clinical trials taking place to see if the early promise we see here will translate into real hope for all those families currently affected by Dravet Syndrome."

What will the Phase Three trial confirm?

A larger randomized Phase Three study is enrolling now. If efficacy and safety hold, zorevunersen would become the first approved therapy for Dravet syndrome that addresses the underlying SCN1A haploinsufficiency (the half-dose of gene function that drives disease) rather than the downstream seizure phenotype.

Regulators will weigh the Phase Three read-out, which the investigators cite as the next decisive milestone, with planned cognitive endpoints measured alongside seizure counts.