British scientists say an experimental drug is showing remarkable promise for children with Dravet syndrome – a severe and hard-to-treat genetic form of epilepsy – after clinical trials suggested that the treatment zorevunersen could cut seizures by as much as 91% while also improving quality of life for many patients.
The therapy works by boosting the function of a key gene involved in nerve cell signalling.
The encouraging results have led researchers to launch a larger phase 3 trial.
They said the treatment appears to be both safe and highly effective, according to the results from the international clinical trial led by UCL (University College London) and Great Ormond Street Hospital (GOSH).
The study, published in The New England Journal of Medicine, found that children afflicted with the syndrome experienced seizure reductions of up to 91%, and suggested that early evidence showed the therapy might also ease some of the disorder’s effects on thinking and behaviour.
Over a three-year period, children participating in the study showed improvements in quality of life, and most reported only mild side effects.
Understanding Dravet syndrome
The rare and severe genetic epilepsy causes frequent seizures that are often difficult to control. The condition is also linked to long term neuro-developmental challenges, feeding problems, movement difficulties, and a higher risk of premature death.
For many families, treatment options remain limited. Existing medications fail to fully control seizures in many patients, and no currently approved therapies directly address the cognitive and behavioural complications associated with the disorder.
Targeting underlying genetic cause
Zorevunersen (produced by Stoke Therapeutics in collaboration with Biogen) is designed to address the root cause of Dravet syndrome by acting on a faulty gene.
Most people carry two copies of the SCN1A gene. In individuals with Dravet syndrome, one copy does not produce enough of a protein needed for proper nerve cell signalling.
The drug works by increasing production of this protein from the healthy copy of the SCN1A gene. By boosting protein levels, the therapy aims to restore more normal function in nerve cells.
Results and ongoing research
The latest findings come from the initial trial and follow up extension studies, which involved 81 children in the United Kingdom and the United States.
These early studies were primarily designed to assess the safety and tolerability of zorevunersen. Researchers also monitored how the treatment affected seizure frequency, cognitive function, behaviour, and overall quality of life. A larger Phase Three trial is currently under way to further evaluate the drug.
Lead author Professor Helen Cross, Director and Professor of Childhood Epilepsy at the UCL Institute of Child Health and an Honorary Consultant in Paediatric Neurology at GOSH, 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.
Numerous seizures
A total of 81 children aged from two to 18 took part in the initial clinical trial. Before starting treatment, they experienced an average of 17 seizures each month.
They received doses of up to 70mg of zorevunersen through a lumbar puncture, some getting a single dose, while others were given additional doses two or three months later during a six-month treatment period.
A total of 75 of the children later continued into extension studies, where they received the medication every four months.
Among those who received the 70mg dose during the first stage of the trial, seizure frequency dropped between 59% and 91% during the first 20 months of the extension studies compared with the number of seizures recorded before treatment began.
Nineteen participants were treated at hospitals in the United Kingdom, and Dravet Syndrome UK Chair of Trustees Galia Wilson said they were looking forward to the phase 3 clinical trials, "to see if the early promise we see here will translate into real hope for the families affected by Dravet Syndrome”.
Study details
Zorevunersen in Children and Adolescents with Dravet Syndrome.
Linda Laux, Joseph Sullivan, Scott Perry, et al.
Published in The New England Journal of Medicine on 4 March 2026
Abstract
Background
Dravet syndrome is a severe developmental and epileptic encephalopathy caused primarily by SCN1A haplo-insufficiency. Risks of sudden unexpected death in epilepsy and cognitive deficits are higher among patients with this syndrome than in the general population with epilepsy. The effects of zorevunersen, an antisense oligonucleotide designed to up-regulate NaV1.1 sodium channels, in patients with Dravet syndrome are not known.
Methods
We enrolled patients two to 18 who were receiving standard anti-seizure medications in two phase 1–2a, open-label, multicentrestudies (MONARCH and ADMIRAL). Patients were included in either a single-ascending-dose cohort, in which zorevunersen (10 to 70 mg) was administered on day 1 only, or a multiple-ascending-dose cohort, in which zorevunersen (20 to 70 mg) was administered two or three times in a 3-month period. Patients eligible for rollover to the two open-label extension studies (SWALLOWTAIL and LONGWING) continued to receive zorevunersen (≤45 mg) every four months. The safety and pharmacokinetics of zorevunersen were assessed in the primary analysis; clinical effects were also evaluated.
Results
A total of 81 patients were enrolled in the phase 1–2a studies. As of May 30, 2025, a total of 75 patients had entered the extension studies. Most adverse events were mild or moderate. The most common adverse event was post–lumbar puncture syndrome (in 25% of patients) in the phase 1–2a studies and was an elevated protein level in cerebrospinal fluid (in 45%) in the extension studies. One patient had suspected unexpected serious adverse reactions, one had an adverse event that led to study withdrawal, two died from sudden unexpected death in epilepsy, and one died from malnutrition. Patients who received 70 mg of zorevunersen (one, two, or three doses) in the phase 1–2a studies, followed by up to 45 mg in the extension studies, had a median change from baseline in convulsive-seizure frequency ranging from −58.82% to −90.91% across 1-month intervals during the first 20 months of the extension studies. The data supported improvements in overall clinical status, quality of life, and adaptive behaviour with continued treatment for up to 36 months in the extension studies.
Conclusions
The safety profile and initial clinical improvement support the continued development of zorevunersen as a potential disease-modifying treatment for Dravet syndrome.
NEJM article – Zorevunersen in Children and Adolescents with Dravet Syndrome (Open access)
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