Dravet syndrome is a rare and severe genetic epilepsy known to cause frequent seizures that are difficult to control. The condition has been linked to long-term neurodevelopmental challenges, feeding problems, difficulties in movement, and a higher risk of premature death.
Most people carry two copies of the SCN1A gene. Among those with Dravet syndrome, however, one copy produces insufficient levels of a protein required for proper nerve cell signaling. Zorevunersen works by increasing production of this protein from the healthy SCN1A gene to restore normal nerve cell signaling. How the drug works in patients with Dravet syndrome has been unknown.
For the current study, researchers conducted phase 1-2a trials involving 81 patients aged 2 to 18 years with Dravet syndrome in the UK and the US. Patients received doses of up to 70 mg of zorevunersen via lumbar puncture. Some received just one dose while others received extra doses two or three months later over a six-month period. Seventy-five children continued into extension studies, where they received the medication every four months.
Among patients who received the 70mg dose during the first stage of the trial, seizure frequency fell by 59- 91% in the extension studies’ first 20 months compared to seizures recorded before treatment began. Before treatment, patients experienced an average of 17 seizures each month.
The researchers further reported improvements in quality of life and adaptive behavior with continued treatment for up to 36 months in the extension studies.
"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,” said lead author of the study Professor Helen Cross, Director and Professor of Childhood Epilepsy at University College London, said in a press release.
"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,” she added.
Sources: Science Daily, New England Journal of Medicine
