An international trial led by University College London and Great Ormond Street Hospital has highlighted an experimental drug, zorevunersenwhich disrupts the daily lives of children affected by rare genetic epilepsy. In some, the number of attacks was reduced by almost 90%, an unprecedented figure in this disease.
The treatment remains in the evaluation phase, but the first results published in the New England Journal of Medicine
talk about a potentially “disease-modifying” therapy for
Dravet syndrome. Behind these medical terms lie calmer nights, motor progress and families who begin to plan ahead again.
Dravet: childhood epilepsy with seizures that are difficult to control
Dravet syndrome is a severe epileptic encephalopathy that affects approximately one in 15,000 babies, causes frequent seizures, developmental delays, feeding and movement disorders, with a high risk of premature death. Available medications poorly control seizures in many children, and there are no medications approved to treat the serious cognitive and behavioral consequences of the disease.
We normally have two copies of the SCN1A gene, but in most people with Dravet syndrome, just one copy of this gene does not produce enough protein for their nerve cells to function properly. Zorevunersen, developed by Stoke Therapeutics with Biogen, acts directly on the genetic cause.
Administered by lumbar puncture, it increases the production of the protein from the healthy copy of the SCN1A gene in order to restore more normal functioning of nerve cells. The goal is to reduce seizures, but also the long-term cognitive and behavioral impact.
A trial on 81 children: up to 91% fewer seizures
In total, 81 children aged 2 to 18 years with Dravet syndrome received up to 70 mg of zorevunersen, in one or more injections, while they had an average of 17 attacks per month. In those who received 70 mg, the frequency of seizures decreased from 59% to 91% over the first 20 months of follow-up. Of these patients, 75 participated in extension studies. These patients continued to receive the drug every four months.
For Professor Helen Cross, lead author, “I regularly see patients with difficult-to-treat genetic epilepsies whose consequences extend far beyond the seizures, and it’s heartbreaking when treatment options are limited. This new treatment could allow children with Dravet syndrome to lead much healthier and happier lives. Overall, our results showed that zorevunersen is safe to use and well tolerated by most patients, and warrant further evaluation in the ongoing phase three study.“.
Children’s lives transformed, while waiting for phase 3
These figures are already reflected in daily life. Freddie, 8, followed in Sheffield and originally from Huddersfield, went from having more than a dozen seizures at night to one or two brief seizures lasting a few seconds every three to five days. His mother Lauren confides: “The trial completely changed our lives. We now have a life we never thought possible and, most importantly, it’s a life Freddie can enjoy“.
The majority of observed side effects, such as headache after lumbar puncture or increased protein in the cerebrospinal fluid, were described as mild or moderate. A large phase 3 study is now underway to confirm the effectiveness and safety of zorevunersen on a larger number of children and to specify which profiles benefit the most, a key step before any possible wide availability.
Galia Wilson, Chair of the Board of Dravet Syndrome UK, said: “We regularly see the devastating impact of this disease on the lives of families. This is why we are so excited about these latest results from the first clinical trials of zorevunersen.
We look forward to phase three clinical trials to see if the promising early results we are seeing will translate into real hope for all families currently affected by Dravet syndrome.“.