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 UCL (University College London) and Great Ormond Street Hospital. The findings suggest the treatment could significantly improve the health and daily lives 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 regularly receiving an investigational drug called zorevunersen.
Researchers also reported early evidence that the therapy may help ease some of the disorder’s effects on thinking and behavior. Over a three year period, children participating in the study showed improvements in quality of life, and most reported side effects were mild.
Understanding Dravet Syndrome
Dravet syndrome is a rare and severe genetic epilepsy that causes frequent seizures that are often difficult to control. The condition is also linked to long term neurodevelopmental 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 behavioral complications associated with the disorder.
How the Drug Targets the 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 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 function in nerve cells.
Clinical Trial Results and Ongoing Research
The latest findings come from the initial 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 assess 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 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 Great Ormond Street Hospital (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.
“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 starting treatment, these patients experienced an average of 17 seizures each month.
Participants received doses of up to 70mg of zorevunersen through a lumbar puncture. Some children received a single dose, while others were given additional doses two or three months later during a six month treatment period.
Seventy five 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 percent and 91 percent during the first 20 months of the extension studies compared with the number of seizures recorded before treatment began.
Hospitals Involved in the Study
Nineteen participants were treated 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 GOSH, the study took place at the National Institute of Health and Care Research’s Clinical Research Facility, a specialized center dedicated to running experimental clinical trials involving children.
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 who receives care through Sheffield Children’s NHS Foundation Trust, participated in the trial.
After starting the treatment in 2021, Freddie’s seizure pattern changed dramatically. He went from experiencing more than a dozen seizures during the night to having just one or two brief seizures lasting only 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.”