Life-changing drug identified for children with rare epilepsy

In a new paper published in The New England Journal of Medicine, the researchers found that children with Dravet syndrome had up to 91% fewer seizures while being regularly administered a new medication called zorevunersen.

The results also show, for the first time, the potential to reduce the impact of the condition on a child’s neurodevelopment and behaviour. The children’s quality of life improved over a three-year period and most of the treatment’s side effects were mild.

Dravet syndrome is a devastating genetic condition which causes frequent, hard-to-control seizures and long-term neurodevelopmental impairment. The condition also causes feeding difficulties, movement problems and has a high risk of premature death. Current treatments fail to control seizures in most patients and there are no approved medicines that address the condition’s devastating cognitive and behavioural impacts.

Zorevunersen (produced by Stoke Therapeutics in collaboration with Biogen) works by tackling the underlying cause of the disease – a faulty gene.

Humans typically have two copies of the SCN1A gene and in most people with Dravet syndrome, one copy of this gene doesn’t produce enough of a protein for their nerve cells to function properly.

Zorevunersen works by increasing the levels of the protein produced by the healthy SCN1A gene, aiming to restore proper nerve-cell function.

The researchers have now published the latest results of their initial trial and extension studies which have involved 81 children with Dravet syndrome in the UK and US.

The published data are from initial studies designed primarily to evaluate the safety and tolerability of zorevunersen. The researchers also evaluated its effects on seizures, cognition, behavior and quality of life. A Phase Three study is currently underway to further evaluate the treatment.

Lead author Professor Helen Cross, Director and Professor of Childhood Epilepsy at the UCL Great Ormond Street 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.

"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.”

Eighty-one children aged two to 18 took part in the initial trial. Patients in these studies had an average of 17 seizures per month before the trials started.

The 81 children were given up to 70mg of zorevunersen by lumbar puncture, either as a single dose or with additional doses two or three months later over a six-month period.

Of those patients, 75 went on to take part in extension studies. Those patients continued to receive the drug every four months.

Patients given a 70mg dose in the initial phase of the trial saw their seizures reduce by between 59 per cent and 91 per cent over the first 20 months of the extension studies compared with the number of seizures they were having before the trial started.

Nineteen of the trial participants were patients at UK hospitals. As well as GOSH, those hospitals were Sheffield Children’s Hospital, Evelina London Children’s Hospital and The Royal Hospital for Children in Glasgow.

At GOSH, the trial was conducted at the National Institute of Health and Care Research’s Clinical Research Facility, which is a state-of-the-art facility dedicated to children taking part in experimental 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.”

6-year-old Jorge, from Las Palmas de Gran Canaria, was diagnosed with Dravet syndrome when he was just five months old after having seizures. Dad Juan said taking part in the trial at GOSH had “drastically” changed Jorge’s life for the better.

Dad Juan said: “Jorge was really susceptible to the smallest thing triggering his seizures such as a cold wind, whereas since taking part in the trial he can now jump into the cold sea!”

Jorge started taking part in the trial and received his first dose in January 2023.

Dad Juan continued: “Taking part in the trial has been life-changing, we now have a normal family life. It’s given Jorge his childhood back and he can take part in activities like his friends. We’re still careful and monitor his temperature, as previously even a small change could trigger a seizure, but we’re no longer on edge. He can go to school by himself and stay with family members. We also decided to have a second baby, who’s now two years old, as Jorge is doing so well.”