Bedford, Mass. — Stoke Therapeutics said it has completed a meeting with the U.S. Food and Drug Administration to align on key aspects of its planned New Drug Application for zorevunersen, an investigational treatment for Dravet syndrome.
The biotechnology company said the meeting covered five years of clinical safety and efficacy data from its Phase 1/2a and ongoing open-label extension studies, as well as the timing and content of the planned NDA submission.
Stoke also discussed how it will analyze Vineland-3 data, a key secondary endpoint in the Phase 3 EMPEROR study.
Following the meeting, the company plans to use a multicomponent assessment of four prespecified Vineland-3 subdomains to evaluate changes in cognition and behavior. The subdomains are expressive communication, receptive communication, interpersonal relationships and personal skills.
The company said the four areas were selected based on feedback from clinicians and caregivers and their potential to demonstrate meaningful effects during the one-year treatment period.
For the U.S. NDA submission, the Vineland-3 subdomain data will be analyzed using a multivariate mixed model for repeated measures.
Stoke plans to continue engaging with the FDA and submit data during the first half of 2027. A Phase 3 readout is expected in the third quarter of 2027, followed by completion of the U.S. NDA submission in the second half of the year.
The company said the timeline could support a potential U.S. approval and launch of zorevunersen in early 2028.
“We are encouraged by our productive dialogue with the FDA and the Agency’s deepening understanding of the severity of Dravet syndrome and need for better treatments, and 5 years of safety and efficacy data for zorevunersen,” said Ian F. Smith, Chief Executive Officer and Director of Stoke Therapeutics.
“We are pleased with the Agency’s willingness to accept a multicomponent assessment of Vineland-3 data measuring changes in cognition and behavior from patients treated in the Phase 3 EMPEROR study. We believe this is the most appropriate way to capture the effects of zorevunersen on people with Dravet syndrome who experience a wide range of debilitating neurodevelopmental impacts,” Smith added.
In the Phase 3 EMPEROR study, participants are randomized 1:1 to receive either zorevunersen through intrathecal administration or a sham comparator over a 52-week treatment period.
The primary endpoint is change from baseline in major motor seizure frequency at Week 28, with all study data also analyzed at Week 52.
Key secondary endpoints include durability of the effect on seizure frequency at Week 52 and changes in adaptive functioning, including cognition and behavior.
Additional endpoints include safety, Clinician Global Impression of Change, Caregiver Global Impression of Change, Bayley Scales of Infant Development and the EuroQol Visual Analog Scale.
