BEDFORD, Mass. — October 5, 2026
Stoke Therapeutics, Inc. announced the completion of a successful meeting with the U.S. FDA to align on key aspects of its planned New Drug Application (NDA) for zorevunersen, an investigational medicine for Dravet syndrome. The discussion covered the five years of clinical safety and efficacy data generated from Phase 1/2a and ongoing open-label extension studies, as well as the planned NDA submission strategy and analysis of the Vineland-3 adaptive functioning data. Stoke expects the Phase 3 EMPEROR study to read out in the third quarter of 2027, supporting completion of the planned U.S. NDA submission in the second half of 2027.
Vineland-3 Analysis to Evaluate Cognitive and Behavioral Effects
Following discussions with the FDA, Stoke will use a multicomponent assessment of four prespecified Vineland-3 subdomains to evaluate changes in cognition and behavior in the Phase 3 EMPEROR study. The analysis will simultaneously assess expressive communication, receptive communication, interpersonal relationships and personal skills using a multivariate mixed model for repeated measures (MMRM). The four subdomains were selected based on input from clinicians and caregivers and their potential to capture meaningful effects during the one-year treatment period. The adaptive functioning endpoint is a key secondary endpoint in EMPEROR and will be evaluated at Week 52.
EMPEROR Phase 3 Study Advances Toward 2027 Readout
The Phase 3 EMPEROR study is evaluating zorevunersen in children aged 2 to less than 18 years with Dravet syndrome and a confirmed SCN1A variant not associated with gain-of-function. Participants are randomized 1:1 to receive intrathecal zorevunersen or a sham comparator for a 52-week treatment period. The primary endpoint is the change from baseline in log-transformed major motor seizure frequency at Week 28, while key secondary endpoints include durability of seizure control at Week 52 and change in adaptive functioning. Stoke completed enrollment in the U.S., U.K. and Japan in June 2026, with additional European enrollment completed in August. Enrollment is also underway in China, with completion anticipated in the second half of 2026.
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Zorevunersen Targets Underlying Dravet Biology
Zorevunersen is an investigational antisense oligonucleotide designed to increase production of functional NaV1.1 protein from the unaffected copy of the SCN1A gene. Stoke’s TANGO approach is intended to restore naturally occurring protein expression and address the underlying biology of Dravet syndrome rather than solely suppressing seizures. Zorevunersen has received FDA and EMA Orphan Drug designations, as well as FDA Rare Pediatric Disease and Breakthrough Therapy designations. The company is targeting a Phase 3 data readout in Q3 2027, followed by completion of the U.S. NDA submission in the second half of 2027. If development and regulatory review progress as planned, Stoke is targeting a potential U.S. approval and launch of zorevunersen in early 2028.
Source: Stoke Therapeutics press release
