Stoke Therapeutics (NASDAQ:STOK) said its Phase III EMPEROR study of zorevunersen in patients with Dravet syndrome remains on track for a data readout in the third quarter of 2027, following completion of enrollment ahead of the company’s planned rolling new drug application submission.
The global, double-blind, sham-controlled study enrolled 162 patients in 10 months, exceeding the company’s target of at least 150 participants. Chief Executive Officer Ian Smith said the enrollment pace reflected awareness of the investigational treatment and interest in its potential to address the genetic cause of Dravet syndrome.
EMPEROR Study Progress
Chief Medical Officer Dr. Barry Ticho said more than 140 EMPEROR participants had passed the week-eight milestone and received either two 70-milligram loading doses of zorevunersen or sham treatment. More than half of enrolled patients had only one dose remaining in the 52-week treatment period, while about 60 participants had completed their week-28 visit.
The study’s primary endpoint is the percentage change in major motor seizure frequency at week 28. Key secondary endpoints assessing cognition and behavior will be measured at week 52, and the trial will remain blinded through that point.
“Thus far, no patients have discontinued treatment in EMPEROR,” Ticho said. He added that the company’s statistical assumptions had included patient discontinuations and a smaller enrollment population than ultimately enrolled, factors management said reinforced its confidence in the study’s statistical powering.
Stoke plans to meet with the FDA in the fourth quarter in a pre-NDA meeting. Smith said discussions are expected to include the sequencing of the rolling application, the study’s statistical analysis plan and the company’s long-term open-label extension data. The company expects to discuss whether secondary endpoints should be analyzed hierarchically or through a composite analysis of Vineland-3 adaptive behavior domains.
Beyond the pivotal population, Stoke expects an additional European cohort of about 30 patients to complete enrollment in August. It also plans to begin a study in infants and toddlers younger than 24 months later this year, intended to support earlier intervention. A separate adult study is also expected to begin by year-end.
Long-Term Zorevunersen Data and Commercial Preparation
Stoke highlighted data from its ongoing open-label extension studies, in which patients have received zorevunersen on top of standard anti-seizure medicines. Ticho said the data showed durable seizure reductions through four years, along with statistically significant improvements in cognition and behavior, as measured by Vineland-3, in each year through four years compared with open-label extension baseline.
The company said more than 930 doses have been administered across its clinical programs, with certain patients treated for more than five years. Of the 81 patients enrolled in the Phase I/IIa study, 75 entered the open-label extension and 57 remain in the studies. Ticho said no new safety findings had emerged and zorevunersen continued to be generally well tolerated.
Chief Patient Officer Jason Hoitt said the company estimates there are approximately 38,000 people with Dravet syndrome across the seven major markets included in the EMPEROR program, including an estimated 16,000 patients in the U.S. Stoke estimates roughly 6,000 U.S. patients are younger than 25 and likely under pediatric care, making them immediately addressable at a potential launch.
Hoitt said about half of identified U.S. patients are treated at the top 50 sites, all of which have experience administering intrathecal medicines. Half of those sites are participating in a zorevunersen study. Stoke expects to use a commercial organization of approximately 25 sales representatives if zorevunersen is approved.
The company recently completed commercial-scale manufacturing validation for both drug substance and drug product and is finalizing product specifications. Hoitt said Stoke continues to expect a broad Dravet syndrome label if approved, consistent with the therapy’s breakthrough designation.
Pipeline Updates
Stoke is also advancing STK-002, an investigational treatment for autosomal dominant optic atrophy, or ADOA, a genetic disorder involving optic nerve degeneration and progressive vision loss. The company said there are currently no approved treatments for ADOA.
The Phase I dose-escalation study in the U.K. and Europe completed dosing in its first cohort of three patients. A safety monitoring committee cleared the program to proceed to a second, higher-dose cohort, with third and fourth cohorts planned subject to continuing safety reviews. Stoke expects early safety and efficacy results in the first half of 2027.
In addition, Smith said Stoke is continuing preclinical work in SYNGAP1-related disorders, where it has five potential drug candidates under evaluation. The company expects to select a development candidate in 2027. Stoke also appointed Tom McCauley as chief scientific officer in July to support platform expansion and translational research.
Cash Position
Chief Financial Officer Tommy Leggett said Stoke ended the second quarter with $354.3 million in cash, cash equivalents and marketable securities. After the quarter ended, the company raised $65.7 million in net proceeds through its at-the-market program by selling about 2.1 million common shares.
That financing brought Stoke’s pro forma cash position to approximately $420 million. Leggett said that, together with reimbursement from Biogen for zorevunersen-related expenses and a potential development milestone payment, the company expects its cash to fund operations through a potential U.S. launch of zorevunersen in early 2028.
About Stoke Therapeutics (NASDAQ:STOK)
Stoke Therapeutics, headquartered in Bedford, Massachusetts, is a clinical-stage biopharmaceutical company focused on developing genetic medicines to upregulate protein production for the treatment of rare neuromuscular and neurological disorders. Founded in 2014, the company applies its proprietary Targeted Augmentation of Nuclear Gene Output (TANGO™) platform to design antisense oligonucleotides that selectively modulate RNA splicing and enhance expression of functional proteins.
The company’s lead program, STK-001, is an antisense oligonucleotide therapy designed to increase production of the sodium channel protein SCN1A and is currently in clinical development for Dravet syndrome, a severe childhood-onset epilepsy.
