Life-changing drug identified for children with rare epilepsy in new research

A new experimental treatment for children with a hard-to-treat form of epilepsy is safe and can reduce seizures dramatically, helping them lead much healthier and happier lives, the findings of a UCL (University College London) and Great Ormond Street Hospital-led international clinical trial show.

In a new paper published in The New England Journal of Medicine, the researchers found that children with Dravet syndrome had up to 91 per cent 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 mental processes 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 behavioral 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 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.”

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 l 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.”

Patient’s story

Sheffield Children’s NHS Foundation Trust patient Freddie, aged eight, from Huddersfield, has Dravet syndrome and has taken part in the trial.

Freddie started taking the medication in 2021 and went from more than a dozen seizures in the night to 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."

Reference:

Linda Laux, Joseph Sullivan, M. Scott Perry, Andreas Brunklaus, M.D. https://orcid.org/0000-0002-7728-6903, Archana Desurkar, M.D., John M. Schreiber, M.D., Colin M. Roberts,