Zorevunersen Reduces Seizures in Dravet Syndrome by 91%
The experimental drug zorevunersen has reduced seizure frequency by up to 91% in children with Dravet syndrome. The results of a clinical trial published in the NEJM pave the way for the first truly disease-modifying therapy for this severe genetic epilepsy.
Breakthrough Published in the New England Journal of Medicine
On March 5, 2026, the prestigious scientific journal The New England Journal of Medicine published the results of a Phase 1/2a clinical trial of the experimental drug zorevunersen. The results are remarkable: in patients receiving a 70 mg dose, the median reduction in convulsive seizure frequency ranged from 58.8% to 90.9% during the first 20 months of extension studies, reaching a 91% reduction in the best monthly interval.
The study included 81 children aged 2 to 18 years with diagnosed Dravet syndrome in the United Kingdom and the United States — specifically within the MONARCH and ADMIRAL studies. Before starting treatment, patients experienced an average of 17 seizures per month.
What is Dravet Syndrome and Why is it so Difficult to Treat?
Dravet syndrome is one of the most severe forms of epilepsy in childhood. It affects approximately one in 16,000 children and is caused by a mutation in the SCN1A gene, which encodes sodium channels essential for proper nerve signaling. Seizures begin in the first year of life, are difficult to control, and lead to significant cognitive and developmental consequences. Existing antiepileptic drugs — such as valproate, clobazam, or fenfluramine — can only partially suppress seizures and often have serious side effects.
How Zorevunersen Works
Zorevunersen is an antisense oligonucleotide — a short synthetic strand of nucleic acids that specifically affects gene expression. In Dravet syndrome, one copy of the SCN1A gene does not function properly, and the brain therefore produces a deficiency of the NaV1.1 protein, a key sodium channel in inhibitory neurons. Zorevunersen binds to a specific section of RNA of the healthy copy of the gene and stimulates increased production of functional protein.
In other words: the drug does not cure the damaged gene, but activates the healthy one to compensate for its failure. This mechanism is crucial — it distinguishes zorevunersen from mere symptomatic treatment and offers the potential for true disease modification.
Safety and Other Benefits of Treatment
Most adverse effects were mild or moderate. The most common problem after administration — the drug is administered intrathecally, directly into the cerebrospinal fluid — was post-lumbar puncture syndrome in 25% of patients in Phase 1/2a. In extension studies, 45% of patients experienced an increase in protein levels in the cerebrospinal fluid, which did not require discontinuation of treatment.
In addition to reducing seizures, the study recorded improvements in cognitive function, behavior, and overall quality of life for patients and their families — which is extremely valuable in Dravet syndrome, as the disease strongly affects the child's entire psychomotor development.
What's Next: The Path to Registration
The drug is being co-developed by Stoke Therapeutics and Biogen. The Phase 3 registration study, called EMPEROR, is currently underway in the USA, the United Kingdom, and Japan and plans to enroll approximately 150 patients. Results are expected in mid-2027 and should serve as the basis for submitting a registration application to the US FDA. A parallel approval process in Europe is anticipated in the same timeframe.
For families of children with Dravet syndrome, this is the biggest therapeutic breakthrough in recent years. However, even the most optimistic scenario does not mean a drug available before 2028 — the path from promising data to approved and reimbursed therapy is always long and full of obstacles in neurology.
