Zorevunersen Phase 3 Study for Dravet Syndrome to Focus on Seizure Control and Adaptive Function
KEY TAKEAWAYS
- The phase 3 EMPEROR study is evaluating the effect of zorevunersen treatment on both major motor seizure frequency and adaptive functioning in children with Dravet syndrome.
- Cognition and behavior will be assessed using Vineland-3 domains covering expressive and receptive communication, interpersonal relationships, and personal skills.
- If positive, the study could clarify whether treatment with zorevunersen is associated with benefits beyond seizure reduction in children with SCN1A-related Dravet syndrome.
Stoke Therapeutics announced completion of a meeting with the Food and Drug Administration (FDA) addressing key elements of a planned New Drug Application (NDA) for zorevunersen (STK-001; Stoke Therapeutics, Bedford, MA), an antisense oligonucleotide under evaluation for the treatment of children with Dravet syndrome. According to a statement from Stoke Therapeutics, the regulatory discussion covered available safety and efficacy data from phase 1/2a and open-label extension studies, as well as the analysis plan for the phase 3 EMPEROR study (NCT06872125).
A key point reported from the meeting involved how cognition and behavior will be evaluated in the study. Stoke plans to use a multicomponent analysis of 4 prespecified Vineland-3 subdomains: expressive communication, receptive communication, interpersonal relationships, and personal skills. These measures will form the second key secondary endpoint at week 52.
Phase 3 EMPEROR Study Details
- EMPEROR is a global, double-blind, sham-controlled study in children aged 2 to <18 years with Dravet syndrome and a confirmed SCN1A variant not associated with gain of function.
- Participants are randomized 1:1 to intrathecal zorevunersen or sham treatment for 52 weeks.
- The primary endpoint is change from baseline in major motor seizure frequency at week 28.
- Key secondary endpoints include durability of seizure-frequency response at week 52 and change in adaptive functioning at week 52.
- Additional measures include clinician- and caregiver-reported global change, Bayley Scales of Infant Development, and quality-of-life assessment.
For neurologists treating people with Dravet syndrome, the regulatory plan is notable because the phase 3 program is evaluating both seizure control and neurodevelopmental functioning. Zorevunersen is not FDA approved, and clinical benefit will depend on the results of the ongoing EMPEROR study.
Source
Stoke Therapeutics. Stoke Therapeutics announces completion of successful meeting with the FDA to align on planned U.S. NDA for zorevunersen, an investigational medicine for the treatment of Dravet syndrome. News release. October 2026.