Stoke Therapeutics details Dravet cognition analysis after FDA meeting
Stoke plans to combine four Vineland-3 subdomains for its U.S. NDA after a Phase 3 readout expected in the third quarter of 2027.
Adrian Kessler
A planned U.S. drug application will assess four measures of cognition and behaviour together after Stoke Therapeutics, Inc. NASDAQSTOK said Monday its FDA meeting supported that approach for zorevunersen in Dravet syndrome. The company expects a Phase 3 readout in the third quarter of 2027 and plans to finish its submission in the second half of that year.
Stoke's Oct. 5 release says the U.S. Food and Drug Administration was willing to accept a combined analysis of four prespecified Vineland-3 subdomains as a key secondary measure in the EMPEROR trial. The meeting concerned the contents and timing of a planned New Drug Application; it was not a filing or a decision on whether the medicine works.
Stoke is a Bedford, Massachusetts developer of RNA medicines, led by a program intended to raise a protein deficient in many people with Dravet syndrome.
Stoke NASDAQSTOK shares closed at US$25.62 on Nasdaq at 4 p.m. EDT on Oct. 2, before the Monday release. Its Aug. 3 financial update put cash, equivalents and marketable securities at US$420 million after a subsequent share sale and said that sum should fund operations through a potential U.S. launch in early 2028.
Four Vineland Measures Enter the Filing Plan
EMPEROR enrolled 162 children in the U.S., U.K. and Japan for the planned U.S. primary analysis, according to Stoke's June 30 enrollment announcement. Participants are assigned equally to intrathecal zorevunersen or a sham procedure during a 52-week blinded treatment period. Its primary endpoint compares change in major motor seizure frequency against sham at Week 28; Stoke will analyze the full study at Week 52.
The FDA meeting focused on a separate measure: adaptive functioning at Week 52. Stoke says its planned U.S. analysis will combine expressive communication, receptive communication, interpersonal relationships and personal skills using a multivariate mixed model for repeated measures. The ClinicalTrials.gov record, last updated Aug. 24, describes the multicomponent score as a nonparametric rank comparison between the treatment and sham groups, while Stoke's Oct. 5 release sets out the proposed U.S. filing analysis.
The FDA meeting account comes from Stoke's release, which describes a planned submission. The blinded Phase 3 trial has yet to provide a treatment effect, confidence interval or p value.
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"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," Stoke chief executive Ian F. Smith said in the Oct. 5 release.
Stoke said in its Aug. 3 update that no EMPEROR participant had discontinued treatment as of July 31. That observation does not establish how zorevunersen's safety will compare with the sham arm when the study is unblinded. The company also expects Week 52 data to test whether any seizure reduction lasts and whether the adaptive functioning measure changes.
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Existing Medicines Treat Dravet Seizures
The peer set already includes Jazz Pharmaceuticals plc NASDAQJAZZ, whose Epidiolex prescribing information lists seizures associated with Dravet syndrome as an approved use. UCB S.A. EBRUCB lists Fintepla for seizures associated with Dravet syndrome in the U.S. Stoke is seeking evidence for an investigational medicine with a different proposed mechanism; the meeting supplies no head-to-head comparison with either marketed drug.
The iShares Biotechnology ETF NASDAQIBB closed at US$205.29 on Nasdaq at 4 p.m. EDT on Oct. 2, setting a dated sector reference before Stoke's announcement. Neither that ETF close nor Stoke's earlier close measures a Monday response to the FDA meeting.
The next dated test is EMPEROR's third-quarter 2027 readout. Its seizure and adaptive functioning results will determine what clinical evidence Stoke can place in the NDA it aims to complete in the second half of 2027.
