Promising trial results for treatment of Dravet syndrome - Children's National

A study published in the New England Journal of Medicine found that children and teenagers with Dravet syndrome who were treated with the medication zorevunersen experienced reductions in seizure frequency, more seizure-free days and significant improvements in quality of life and overall functioning.

Why it matters

Dravet syndrome is a rare, severe form of epilepsy that begins in infancy, often with prolonged seizures triggered by fever. It is most commonly caused by mutations in the SCN1A gene and leads to frequent seizures, developmental delays and other neurological challenges. Treatment options remain limited for this lifelong condition.

"In this trial, beyond seizure reduction, we observed improvements in quality of life and overall functioning that were reported by both clinicians and caregivers," said John Schreiber, MD, pediatric neurologist at Children's National Hospital and co-author of the study. "These outcomes are especially meaningful for individuals with Dravet syndrome and their families, given the broad and persistent impact of the disease."

The big picture

Zorevunersen is an antisense oligonucleotide designed to target the SCN1A gene and increase production of the NaV1.1 protein, with the goal of addressing the underlying cause of the disease.

The study, supported by Stoke Therapeutics, enrolled 81 participants with Dravet syndrome between the ages 2 to 18 who were receiving anti-seizure medications into two Phase 1/2a open-label multicenter trials - MONARCH and ADMIRAL. Patients were put into two cohorts, a single-ascending-dose cohort or a multiple-ascending-dose cohort. Of the 81 participants, 75 who completed the Phase 1/2a trials and were eligible enrolled in open-label extension studies - LONGWING and SWALLOWTAIL - where treatment with zorevunersen continued.

The authors noted the median reductions in seizure frequency were largest in patients who received multiple initial doses of 70mg of zorevunersen in the Phase 1/2a trials. Continued treatment in the extension studies was associated with stabilized reductions in the frequency of convulsive seizures through 36 months.

What's next

Zorevunersen is currently being further evaluated in an ongoing Phase 3 clinical study in patients with Dravet syndrome.

Read the study, Zorevunersen in Children and Adolescents with the Dravet Syndrome, in the New England Journal of Medicine.