Stoke Therapeutics' Dravet Trial Enrollment Surpasses Target, No Discontinuations Reported
Stoke Therapeutics (NASDAQ:STOK) said its Phase III EMPEROR study of zorevunersen for Dravet syndrome has enrolled 162 patients, exceeding the trial’s pre-specified target of 150 and reporting no discontinuations to date. Chief Executive Officer Ian Smith disclosed the update at a Canaccord Genuity event, pointing to the enrollment and retention numbers as early evidence of both trial execution and the drug’s tolerability profile.
The sham-controlled study is evaluating zorevunersen in patients already receiving stable background anti-seizure medications. The 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 lack of dropouts stands out in part because the protocol assumed a 15% discontinuation rate, mainly to account for the possibility that control-arm patients might withdraw after undergoing a sham lumbar puncture procedure. Smith said the absence of patient discontinuations so far reflects tolerability and execution, while also noting that the open-label extension may play a role in retention by providing access to zorevunersen after the controlled phase ends.
“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.
The early retention data help de-risk a study that was designed with a 15% dropout cushion. For a rare-disease trial with a sham procedure in the control arm, zero discontinuations through multiple timepoints is an unusually strong sign, though the company remains blinded and the final readout will determine whether clinical benefits match earlier open-label signals. If the trend holds, it could strengthen Stoke’s regulatory discussions and help build the commercial case for a chronic therapy.
The U.S. Food and Drug Administration has granted breakthrough therapy designation for zorevunersen in Dravet syndrome, based in part on seizure reductions and Vineland adaptive behavior outcomes from earlier studies and an open-label extension. Smith said Stoke expects to begin a rolling New Drug Application submission in the first quarter of 2027, pending discussions with the FDA at a planned pre-NDA meeting, and aims to complete the submission in the third quarter of 2027 after the EMPEROR trial finishes. The company plans to submit chemistry, manufacturing and controls information first, followed by preclinical materials and clinical data. Smith also said Stoke intends to discuss whether long-term open-label data can be included in the eventual product label.
While seizure reduction is the primary endpoint, EMPEROR is also designed to assess cognitive and behavioral changes using the Vineland-3 measure. Smith said the assessment captures 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, and natural-history data suggest patients generally do not gain function over time. In prior long-term open-label data, the company observed continued gains in cognitive and behavioral measures over four years, including examples of children progressing from non-verbal to verbal or becoming more ambulatory. Those results were discussed as context from earlier studies rather than findings from the ongoing Phase III trial.
On seizure outcomes, Smith said the Phase III study was powered for a roughly 40% to 45% treatment difference. In earlier Phase I/II studies and the open-label extension, patients in the higher-dose group experienced seizure reductions of 70% to 80% while receiving zorevunersen on top of standard anti-seizure therapies.
Jason Hoitt, Stoke’s chief patient officer, said persistent seizures remain the primary unmet need cited by caregivers and physicians treating Dravet syndrome, followed by quality-of-life and neurocognitive concerns. Hoitt said the company has also completed payer research on the potential value proposition for zorevunersen, with payers indicating that long-term safety and efficacy data would be among the most compelling evidence for a chronic treatment if the therapy reaches approval.
Beyond Dravet syndrome, Stoke is developing a program for autosomal dominant optic atrophy (ADOA), a genetic disease associated with progressive vision loss. Smith said the Phase I/II OSPREY study is a single-dose, dose-escalation trial targeting the OPA1 gene, and will assess visual changes using low-contrast visual acuity and fluorescent fundus autofluorescence. The company expects potential efficacy data from the third and fourth cohorts in the first half of 2027 and, if results support further development, plans to discuss a potential registrational study with the FDA.
Smith also addressed the company’s collaboration with Biogen for territories outside North America. The partnership, in place for roughly 18 months, was designed to broaden Stoke’s capabilities beyond North America and leverage Biogen’s experience with antisense oligonucleotide therapies, manufacturing and international commercial infrastructure.
Stoke Therapeutics, headquartered in Bedford, Massachusetts, is a clinical-stage biopharmaceutical company developing genetic medicines to upregulate protein production for rare neuromuscular and neurological disorders. Founded in 2014, the company uses its Targeted Augmentation of Nuclear Gene Output (TANGO) platform to design antisense oligonucleotides that selectively modulate RNA splicing and enhance expression of functional proteins. Its lead program, zorevunersen, formerly STK-001, is designed to increase production of the sodium channel protein SCN1A and is being developed for Dravet syndrome, a severe childhood-onset epilepsy.