Dravet syndrome treatment shows long-term benefits in early trials

Treatment with the experimental therapy zorevunersen may alter the progression of Dravet syndrome, according to new long-term data from early clinical trials.

The data indicate that zorevunersen led to long-term reductions in seizure rates, improved communication abilities, and overall quality of life, and that the experimental treatment was generally well tolerated. Zorevunersen’s developers, Stoke Therapeutics and Biogen, shared the data in a series of presentations at the 16th European Epilepsy Congress, held Sept. 5-9 in Athens.

“Taken together, the data from studies of zorevunersen offer hope for a very different future for people living with Dravet syndrome and their families,” Helen Cross, PhD, a professor at University College London and an investigator in the zorevunersen trial program, said in a Biogen press release.

Dravet syndrome is caused primarily by mutations in the SCN1A gene. These mutations reduce levels of a brain protein called NaV1.1, disrupting normal brain signaling and causing seizures and other Dravet symptoms.

Zorevunersen is designed to boost the production of the NaV1.1 protein, addressing the underlying molecular defect that drives neurological problems in Dravet syndrome. The therapy is administered by injection into the spinal canal.

Recommended Reading

July 31, 2026 Columns by Sarah Lango

Caring for a medically fragile kid while parenting multiple children

Reduction in seizure rates

The new data come from a pair of Phase 1/2 trials, MONARCH (NCT04442295) and ADMIRAL (ISRCTN99651026), and their respective open-label extensions, SWALLOWTAIL (NCT04740476) and LONGWING (ISRCTN12811235).

In the open-label extensions, all participants received long-term zorevunersen treatment and were monitored for safety and efficacy. Of the 81 patients enrolled in the original Phase 1/2 studies, 75 chose to continue into the open-label extensions, and as of the four-year data cutoff, 58 were continuing to receive zorevunersen in these studies.

Long-term safety data indicate that zorevunersen has been generally well tolerated, with some patients treated for more than five years. Most patients given the therapy have experienced increases in protein levels in the fluid that surrounds the brain, but these increases have not been linked to serious complications.

“For patients with a chronic disease like Dravet syndrome, safety and tolerability are critically important,” said Stephanie Fradette, head of the rare neurology development unit at Biogen. “The ongoing open-label extension studies will continue to grow the body of evidence shaping our understanding of zorevunersen’s long-term safety as well as its potential to address the underlying genetic cause of Dravet syndrome and improve outcomes for patients.”

In line with earlier results, long-term data suggest that zorevunersen, given with other antiseizure medications, led to a pronounced reduction in seizure rates. The therapy substantially reduced rates of severe seizures associated with sudden unexpected death in epilepsy (SUDEP), which is the leading cause of death for young people with Dravet syndrome.

“Up to 20% of children and adolescents with Dravet syndrome die before reaching adulthood, and SUDEP is the primary cause,” said Barry Ticho, MD, PhD, Stoke’s chief medical officer.

Patients given zorevunersen generally saw improvements on the Vineland-3, a measure of communication abilities and interpersonal skills. By contrast, in external groups of Dravet patients who did not receive zorevunersen, long-term Vineland-3 scores showed little change over the years of follow-up.

“These data are especially meaningful because they show substantial reductions in the severe seizures most strongly correlated with SUDEP and demonstrate continuing improvements in the debilitating neurodevelopmental aspects of the disease,” Ticho said. “Together with ongoing improvements in quality of life, these data increase our confidence in what zorevunersen may one day deliver for the Dravet community.”

After starting zorevunersen, patients experienced long-term improvements in quality of life, as reflected by higher scores on the EuroQol Visual Analog Scale.

“The continuing improvements in cognition and behavior shown in these studies suggest zorevunersen has the potential to narrow the developmental gap between these children and their neurotypical peers, helping them gain more independence and participate in experiences that many thought might never be possible,” Cross said.

Stoke is sponsoring a Phase 3 clinical trial, EMPEROR (NCT06872125), to further test zorevunersen. The study is testing the experimental therapy against a sham in 162 children and adolescents with Dravet syndrome who have had continual seizures despite standard treatment. The study’s main goal is to determine whether zorevunersen is better than the sham at reducing major motor seizures over about seven months.

Results from EMPEROR are expected next year and will form the basis for an application seeking approval of zorevunersen in the U.S.