Stoke Therapeutics' Dravet Trial Tops Enrollment Target With Zero Dropouts

Stoke Therapeutics’ Phase III EMPEROR trial for Dravet syndrome has enrolled 162 patients, surpassing its 150-patient target, with no discontinuations reported so far.

The trial is evaluating seizure reduction at week 28 and cognitive and behavioral outcomes at week 52.

The company plans to provide another trial update near the end of the third quarter and expects to begin a rolling FDA New Drug Application submission in the first quarter of 2027, targeting completion in the third quarter of 2027.

Stoke is also advancing an early-stage treatment for autosomal dominant optic atrophy, with potential efficacy data expected in the first half of 2027, while relying on its partnership with Biogen to support development and commercialization outside North America.

Stoke Therapeutics NASDAQ: STOK said its Phase III EMPEROR study of zorevunersen for Dravet syndrome has enrolled 162 patients, exceeding its target enrollment of 150, with no patient discontinuations reported to date.

Speaking at a Canaccord Genuity event, Chief Executive Officer Ian Smith said the sham-controlled trial is evaluating zorevunersen in patients who are already receiving stable background anti-seizure medications.

The study’s primary endpoint is seizure reduction at week 28, while secondary assessments at week 52 include measures of cognition and behavior.

Smith said 145 of the 162 enrolled patients have passed week eight, approximately 80 have reached week 24, and 60 have completed the week-28 primary endpoint.

Patients receive two 70-milligram doses by week eight, followed by two 45-milligram doses during the 52-week study period, according to Smith.

The company had incorporated a 15% discontinuation assumption into the trial design, partly because the control arm includes a sham lumbar puncture procedure.

Smith said the absence of dropouts so far reflects both trial execution and the drug’s tolerability profile, while noting that some patient retention may also relate to the availability of an open-label extension in which participants can receive treatment after the controlled portion of the trial.

“The drug must be well-tolerated to date. Otherwise, we would have seen dropouts related to the drug,” Smith said. He added that Stoke remains blinded to the trial data.

Stoke expects to provide another update on the EMPEROR study toward the end of the third quarter, Smith said.

Smith said the U.S. Food and Drug Administration granted breakthrough therapy designation for zorevunersen for the treatment of Dravet syndrome, based on data involving both seizure reductions and outcomes from the Vineland adaptive behavior assessments in earlier studies and an open-label extension.

While EMPEROR’s primary endpoint focuses on seizures, the study is also designed to assess cognitive and behavioral changes through the Vineland-3 assessment.

Smith said the measures include receptive and expressive communication, motor skills, interpersonal skills and social functioning.

The trial is powered around the receptive communication endpoint, with Stoke seeking a two- to three-point treatment benefit versus natural history, Smith said.

He said natural-history data suggest that patients generally do not gain function over time.

Smith said prior long-term open-label data showed continued gains in cognitive and behavioral measures over four years, in addition to seizure reduction.

He described examples of children progressing from non-verbal to verbal or becoming more ambulatory, though these outcomes were discussed in the context of the company’s prior data rather than resu...