Promising Results of Investigational Antisense Oligonucleotide Treatment for Dravet Syndrome

New research presented at the American Epilepsy Society (AES) 2024 Annual Meeting reveals promising results for zorevunersen (STK-001; Stoke Therapeutics, Bedford, MA) as a potential treatment for individuals diagnosed with Dravet syndrome (DS). Results from 2 open-label extension (OLE) studies, SWALLOWTAIL (US: NCT04740476) and LONGWING (UK: 2021-005626-14), demonstrate durable reductions in convulsive seizure frequency and clinically meaningful improvements in cognition and behavior over 24 months in individuals with DS given the intrathecally administered drug. Zorevunersen, an investigational antisense oligonucleotide, targets the underlying genetic cause of DS by upregulating Nav1.1 protein expression. The study included 68 patients who received up to 9 doses of zorevunersen (10-45 mg/dose) every 4 months.

Key findings include

• Sustained reductions in convulsive seizure frequency
• Improvements across multiple Vineland-3 subdomains
• Consistent positive assessments from both caregivers and clinicians

The treatment was generally well-tolerated. 

Lead investigator Joseph Sullivan, MD, from UCSF Weill Institute for Neurosciences, San Francisco, CA, commented, "These results contrast with the natural history of DS, where little change in seizure frequency or cognition is typically observed over time."

The data support plans for maintenance dosing to be studied in a new research project analyzing zorevunersen as a potential first disease-modifying treatment for DS.