An experimental treatment for children with severe and difficult-to-treat epilepsy appears to be safe and highly effective in reducing seizures, according to results from an international clinical trial led by University College London and Great Ormond Street Hospital. The findings suggest that this treatment could significantly improve the health and daily life of affected children.
This study New England Medical Journalfound that children with Dravet syndrome had seizures reduced by up to 91 percent while regularly receiving an investigational drug called zorebnersen.
Researchers also reported early evidence that the treatment may help alleviate some of the disorder’s effects on thinking and behavior. Over three years, the children in the study showed improved quality of life, and most of the side effects reported were mild.
Understanding Dravet syndrome
Dravet syndrome is a rare and severe genetic epilepsy that causes seizures that are often difficult to control. The condition is also associated with long-term neurodevelopmental challenges, feeding problems, mobility difficulties, and an increased risk of early death.
For many families, treatment options remain limited. Existing medications fail to fully control seizures in many patients, and no currently approved treatments directly address the cognitive and behavioral complications associated with the disease.
How drugs target underlying genetic causes
Zorevunersen (manufactured by Stoke Therapeutics in collaboration with Biogen) is designed to address the root cause of Dravet syndrome by acting on the defective gene.
Most people have two copies of the SCN1A gene. People with Dravet syndrome do not produce just one copy of the protein needed for proper nerve cell signaling.
This drug works by increasing the production of this protein from healthy copies of the SCN1A gene. This treatment aims to restore more normal function to nerve cells by increasing protein levels.
Clinical trial results and ongoing research
The latest findings come from an initial trial and follow-up expansion study of 81 children with Dravet syndrome in the UK and US.
These early studies were primarily designed to evaluate the safety and tolerability of zorebnersen. Researchers also monitored how the treatment affected seizure frequency, cognitive function, behavior, and overall quality of life. A large phase 3 trial is currently underway to further evaluate this drug.
Lead author Professor Helen Cross, Director and Professor of Childhood Epilepsy at the UCL Institute of Child Health and Honorary Consultant in Child Neurology at Great Ormond Street Hospital (GOSH), said: “We regularly see patients with this difficult genetic form of epilepsy, and it’s heartbreaking that treatment options are so limited. This new treatment could help children with Dravet syndrome live healthier, happier lives.”
“Overall, our findings demonstrate that zolevnersen is safe to use and well tolerated by most patients, supporting further evaluation in ongoing phase 3 trials.”
Details of the trial
A total of 81 children between the ages of 2 and 18 participated in the first clinical trial. Before starting treatment, these patients experienced an average of 17 attacks per month.
Participants received up to 70 mg of zolevnersen via lumbar puncture. Some children received a single dose, while others received an additional dose two or three months later during the six-month treatment period.
Seventy-five of the children then continued in the extension study, where they received the drug every four months.
For patients who received 70 mg in the first phase of the trial, the frequency of seizures during the first 20 months of the extension trial was reduced by between 59 percent and 91 percent compared to the number of seizures recorded before starting treatment.
Hospitals that participated in the study
Nineteen participants were treated in UK hospitals. Participating centers include Great Ormond Street Hospital, as well as Sheffield Children’s Hospital, Evelina London Children’s Hospital and Glasgow Royal Children’s Hospital.
At GOSH, the study was conducted at the Clinical Research Facility of the National Institute for Health and Care Excellence, a specialized center specialized in conducting experimental clinical trials in children.
Galia Wilson, Chair of Dravet Syndrome UK, said: “We regularly see the devastating impact this disease has on the lives of families, which is why we are so excited about the latest results from the first clinical trial of Zolevensen.”
“We now look forward to the Phase 3 clinical trial being conducted to see if the initial promise seen here translates into real hope for all families suffering from Dravet syndrome.”
patient story
Freddy, an eight-year-old patient from Huddersfield who receives care through Sheffield Children’s NHS Foundation Trust, took part in the trial.
After starting treatment in 2021, Freddie’s seizure patterns changed dramatically. He went from experiencing more than a dozen seizures a night to only having one or two short seizures lasting a few seconds every 3 to 5 days.
His mother, Lauren, said: “This trial has completely changed our lives. We now have a life we never thought was possible and, most importantly, a life Freddie can enjoy.”
