Zorevunersen cut seizures by up to 91% in children with Dravet syndrome over three years

University College London / Great Ormond Street Hospital

Freddie started taking the medication in 2021. Before that, the eight-year-old from Huddersfield, England, had more than a dozen seizures every night. Now he has one or two brief episodes, lasting seconds, every three to five days.

Freddie has Dravet syndrome, a genetic form of epilepsy that begins in infancy and does not respond well to standard treatments. The condition causes more than seizures. Children with Dravet syndrome typically develop cognitive impairments, behavioral difficulties, feeding problems, movement disorders, and face an elevated risk of premature death. No approved treatment addresses anything beyond the seizures, and even seizure control is poor for most patients.

The drug that changed Freddie's life is called zorevunersen, and results from its initial clinical trials have just been published in The New England Journal of Medicine.

Targeting the gene, not just the symptom

Most people carry two copies of the SCN1A gene, which provides instructions for making a protein essential to nerve cell function. In Dravet syndrome, one copy is mutated and fails to produce enough working protein. The result is a brain with roughly half the sodium channel activity it needs.

Zorevunersen, developed by Stoke Therapeutics in collaboration with Biogen, takes a different approach from conventional anti-seizure medications. Instead of damping down brain activity broadly, it increases the protein output from the patient's healthy SCN1A gene, aiming to compensate for the broken copy. The drug is delivered by lumbar puncture directly into the spinal fluid.

The numbers from three years of data

The published results come from two Phase 1/2a open-label studies, one in the UK and one in the US, enrolling 81 children aged 2 to 18 with Dravet syndrome. All were already taking standard anti-seizure medications that were not adequately controlling their symptoms. The average participant had 17 seizures per month before enrollment.

Of the 81 children in the initial trials, 75 continued into open-label extension studies, receiving 45 mg of zorevunersen every four months. Over the first 20 months of extended dosing, patients who had received the highest initial dose (70 mg) saw seizure reductions between 59% and 91%.

For the first time in a Dravet syndrome trial, the researchers also reported improvements beyond seizure control. Children in the extension studies for more than 36 months showed significant gains in expressive and receptive communication. Quality of life improved over the three-year period.

Side effects and safety concerns

Nearly all patients experienced at least one treatment-emergent adverse event, but the majority were mild to moderate. The most common issue in the initial trials was post-lumbar puncture syndrome, occurring in about 25% of patients. In the extension studies, the most frequent finding was an increase in cerebrospinal fluid protein levels, seen in 45% of participants. However, none of those patients developed increased intracranial pressure or hydrocephalus.

Only one serious adverse event was considered related to the treatment. The drug is delivered by spinal injection, which carries its own procedural risks and requires clinical settings for administration, typically every four months.

What the data can and cannot show

These were Phase 1/2a studies, designed primarily to evaluate safety and tolerability rather than efficacy. There was no placebo control group. All participants knew they were receiving the active drug, which means the reported improvements in quality of life and behavior could be influenced by expectation effects.

The sample size of 81 children is small, and the open-label extension design means the strongest responders may have been more likely to continue, potentially inflating the long-term efficacy numbers.

A Phase 3, double-blind, placebo-controlled trial is currently underway. That study will provide the controlled comparison needed to determine how much of the observed benefit is genuinely attributable to the drug.

Still, for a condition where existing treatments fail most patients and no approved therapy addresses the cognitive and developmental dimensions of the disease, the early signal is striking. If the Phase 3 data hold up, zorevunersen would represent the first treatment for Dravet syndrome that goes after the genetic root rather than managing symptoms one at a time.