Stoke Therapeutics completes an FDA meeting on its planned U.S. NDA for zorevunersen, with guidance on EMPEROR cognition, behavior and seizure analyses.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Stoke Therapeutics has completed a meeting with the U.S. Food and Drug Administration (FDA) to discuss key aspects of its planned New Drug Application (NDA) for zorevunersen, an investigational medicine being developed for Dravet syndrome. The meeting included discussions on five years of clinical safety and efficacy data from Phase 1/2a and ongoing open-label extension studies, along with the planned analysis of cognition and behavior outcomes in the Phase 3 EMPEROR study.
FDA Guidance on Cognition and Behavior Assessment
Following FDA feedback, Stoke plans to use a multicomponent assessment comprising four prespecified Vineland-3 subdomains in the EMPEROR study. These include expressive communication, receptive communication, interpersonal relationships and personal skills.
The company selected these subdomains based on feedback from clinicians and caregivers and their potential to demonstrate meaningful effects during the one-year EMPEROR treatment period. For the planned U.S. NDA, the four Vineland-3 subdomains will be analyzed together using a multivariate mixed model for repeated measures (MMRM).
Phase 3 EMPEROR Study
The Phase 3 EMPEROR study (NCT06872125) is a global, double-blind, sham-controlled study 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 zorevunersen by intrathecal administration or a sham comparator for a 52-week treatment period following baseline.
The primary endpoint evaluates change from baseline in log-transformed major motor seizure frequency at Week 28. The study also assesses the durability of the treatment effect on major motor seizure frequency at Week 52 and changes from baseline in adaptive functioning, including cognition and behavior, at Week 52.
Key Clinical Assessments
For the planned U.S. analysis, MMRM will be used to estimate treatment effects using data collected from baseline through Week 52. The primary treatment effect will be estimated from the change in seizure frequency at Week 28, based on the four-week interval from Week 24 to Week 28.
The second key secondary endpoint will assess changes in adaptive functioning at Week 52 using the four prespecified Vineland-3 subdomains together. Other assessments include safety, Clinical Global Impression of Change (CGI-C), Caregiver Global Impression of Change (CaGI-C), Bayley Scales of Infant Development (BSID-IV) and the EuroQol Visual Analogue Scale (EQ-VAS).
Progress Toward the Planned U.S. NDA
Stoke plans to continue engaging with the FDA and submit data during the first half of 2027. The Phase 3 EMPEROR readout is anticipated in the third quarter of 2027, after which the company plans to complete its U.S. NDA submission during the second half of 2027.
The timeline could support a potential U.S. approval and launch of zorevunersen in early 2028. However, this remains a projected development timeline and does not indicate that approval has been granted or assured. Zorevunersen remains investigational, and its safety and efficacy have not been evaluated by any regulatory authority.
Zorevunersen and Dravet Syndrome
Zorevunersen is an investigational antisense oligonucleotide designed to increase functional NaV1.1 protein production in brain cells from the unaffected wild-type copy of the SCN1A gene. Stoke is developing the therapy as a potential disease-modifying treatment for Dravet syndrome.
Dravet syndrome is a severe genetic developmental and epileptic encephalopathy characterized by recurrent seizures and significant cognitive and behavioral impairments. Most cases are associated with a mutation in one copy of the SCN1A gene, which can result in insufficient NaV1.1 protein. The condition may also affect intellectual development, language and speech, movement and balance, growth, sleep, mood and autonomic function.
The completion of the FDA meeting marks a regulatory planning milestone for Stoke as it prepares for the EMPEROR Phase 3 readout and planned U.S. NDA submission. The next major development milestone is the anticipated Phase 3 readout in the third quarter of 2027.
Reference
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, Stroke Therapeutics, 05 October 2026
A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients With Dravet Syndrome, ClinicalTrials.gov ID NCT06872125
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.
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