Promising Results for Experimental Dravet Syndrome Treatment

Dravet syndrome, a rare form of epilepsy, begins in infancy and causes a lifetime of severe, recurring seizures and cognitive and behavioral impairments. Most treatments focus on preventing seizures, but Children’s Hospital Colorado researchers have evaluated a new treatment with promising results recently published in the New England Journal of Medicine. It’s not only preventing seizures but also improving cognition and behavior.  

“These improvements are not something we typically see in patients with Dravet syndrome,” says Kelly Knupp, MD, Director of the Dravet Syndrome Clinic. “Together, this data is starting to paint a fuller picture of the potential impact disease modification could have on a patient’s overall health and daily living.” 

Researching new treatments 

The team assessed data gathered from multiple studies and evaluating the efficacy, safety and tolerability of zorevunersen, an investigational antisense oligonucleotide discovered by Stoke Therapeutics and developed in collaboration with Biogen. Zorevunersen works by tackling the underlying cause of Dravet syndrome. Most cases of Dravet syndrome are caused by mutations in one copy of a gene called SCN1A, leading to insufficient levels of a certain protein in neuronal cells in the brain. Zorevunersen is designed to increase levels of the protein produced by the healthy SCN1A gene, aiming to restore proper neuronal function. 

In two early-stage studies, 81 patients received at least one dose of zorevunersen, with a median baseline seizure frequency of 17 over a 28-day period. The data showed that patients — especially those who received 70 mg of zorevunersen — had substantial reductions in major motor seizures. These reductions continued through an additional 36 months of open label extension studies for a total of nearly 4 years of treatment. Caregivers and clinicians reported overall improvements with 94.7% of patients ranging from minimally improved to very much improved. 

Treatment with zorevunersen shows promising early results 

At 12, 24 and 36 months of treatment, researchers observed substantial improvements in cognition and behavior. This includes expressive communication, receptive communication, interpersonal relationships, personal skills, coping skills, play and leisure, gross motor skills and fine motor skills. By contrast, data from a separate observational study of children and adolescents with Dravet syndrome showed neurodevelopment plateaued at the developmental age of approximately two. 

“Dravet syndrome impacts more than seizures, these findings give us hope for improvement in all the symptoms of this disease. While there is still more to learn, the safety profile of this treatment looks promising,” says Dr. Knupp. 

Zorevunersen has been well tolerated in the early stage and open label extension studies. The most common adverse event was cerebrospinal fluid protein elevation, with a higher incidence (45%) observed in the open label extension studies. Treatment-emergent serious adverse events were reported in 22% of patients in the early stage and 29% of patients in the open label extension. All except one were unrelated to the drug.  

Improvements in quality of life 

“To have a treatment that may impact more than seizures in this patient population could lead to an improvement in overall quality of life not just for the children but for their families. This safety data is exciting as it allows the treatment to move on to a randomized trial so that efficacy can be assessed,” says Dr. Knupp. 

Researchers are currently enrolling patients in the Phase 3 Emperor study — a major step before applying for FDA approval. Phase 3 data is expected in mid-2027.