Gene-Targeted Therapy Demonstrates Up to 91% Seizure Reduction in Dravet Syndrome
An experimental therapy for children with a severe and difficult-to-treat form of epilepsy appears to be both safe and highly effective at reducing seizures, according to results from an international clinical trial led by University College London (UCL) and Great Ormond Street Hospital. The findings suggest the treatment could significantly improve the health and quality of life of affected children.
The study, published in The New England Journal of Medicine, found that children with Dravet syndrome experienced seizure reductions of up to 91 percent while receiving an investigational drug called zorevunersen.
Researchers also reported early evidence suggesting the therapy may help improve some of the disorder’s cognitive and behavioral effects. Over a three-year period, children participating in the study showed improvements in quality of life, while most reported side effects were mild.
Understanding Dravet Syndrome
Dravet syndrome is a rare and severe genetic form of epilepsy characterized by frequent seizures that are often difficult to control. The condition is also associated with long-term neurodevelopmental challenges, feeding difficulties, movement disorders, and an increased risk of premature death.
For many families, treatment options remain limited. Existing medications often fail to fully control seizures, and no currently approved therapies directly address the cognitive and behavioral complications linked to the disorder.
How the Drug Targets the Underlying Genetic Cause
Zorevunersen, developed by Stoke Therapeutics in collaboration with Biogen, is designed to target the underlying genetic cause of Dravet syndrome.
Most people carry two copies of the SCN1A gene. In individuals with Dravet syndrome, one copy does not produce sufficient amounts of a protein necessary for proper nerve cell signaling.
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 nerve cell function.
Clinical Trial Results and Ongoing Research
The latest findings come from the initial clinical trial and follow-up extension studies, which together involved 81 children with Dravet syndrome in the United Kingdom and the United States.
These early studies were primarily designed to evaluate the safety and tolerability of zorevunersen. Researchers also monitored how the treatment affected seizure frequency, cognitive function, behavior, and overall quality of life. A larger Phase Three trial is currently underway to further assess the therapy.
Lead author Professor Helen Cross, Director and Professor of Childhood Epilepsy at 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."
"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."
Details of the Trial
A total of 81 children between the ages of two and 18 participated in the initial clinical trial. Before beginning treatment, participants experienced an average of 17 seizures per month.
Children received doses of up to 70 mg of zorevunersen through lumbar puncture. Some participants received a single dose, while others received additional doses two or three months later during the six-month treatment period.
Seventy-five children later continued into extension studies, during which they received the medication every four months.
Among participants who received the 70 mg dose during the initial stage of the trial, seizure frequency decreased by between 59 percent and 91 percent during the first 20 months of the extension studies, compared with seizure rates recorded before treatment.
Hospitals Involved in the Study
Nineteen participants received treatment at hospitals in the United Kingdom. In addition to Great Ormond Street Hospital, participating centers included Sheffield Children's Hospital, Evelina London Children's Hospital, and The Royal Hospital for Children in Glasgow.
At Great Ormond Street Hospital, the study was conducted at the National Institute for Health and Care Research Clinical Research Facility, a specialized center dedicated to pediatric experimental clinical trials.
Dravet Syndrome UK Chair of Trustees Galia Wilson 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."
"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."
Patient Story
Freddie, an eight-year-old patient from Huddersfield receiving care through Sheffield Children's NHS Foundation Trust, participated in the trial.
After starting treatment in 2021, Freddie’s seizure pattern changed dramatically. He went from experiencing more than a dozen seizures during the night to having only one or two brief seizures lasting seconds 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."
