Phase 3 Data Readout of EMPEROR Study to Come Earlier, With FDA Submission Expected to Follow

According to a new update from Stoke Therapeutics, data from the company’s massive, phase 3 EMPEROR trial (NCT06872125), a registrational study testing investigational zorevunersen in patients with Dravet syndrome (DS), is expected to come earlier than expected, with results to come mid-2027. The company also noted that it is planning a new drug application (NDA) submission for the potential disease-modifying agent in the first half of 2027, using findings from EMPEROR as supportive evidence.¹

Following positive phase 2 data, EMPEROR was created to further validate the efficacy and safety of zorevunersen, an antisense oligonucleotide, as an effective treatment for DS. The phase 3 trial, which spans 60 weeks, includes 150 patients who have a confirmed variant in the SCN1A gene not associated with a gain of function. EMPEROR, which also includes a follow-up open-label extension, uses change in major motor seizure frequency as the primary outcome.

As part of zorevunersen’s Breakthrough Therapy Designation, the company also held a multidisciplinary meeting with the FDA to review the agent’s ongoing clinical development and to discuss potential opportunities for expedited regulatory pathways. No immediate changes to the development program were agreed upon during the meeting. However, the FDA requested additional information, and discussions remain ongoing as the company and the agency continue to evaluate potential strategies to accelerate zorevunersen’s development, registration, and delivery to patients.

“Our recent multidisciplinary meeting was productive and we appreciate the FDA’s interest in deepening their understanding of Dravet syndrome and its impacts on patients and their families while also taking time to review and discuss our four years of clinical data,” Ian F. Smith, chief executive officer and director of Stoke, said in a statement.¹ “Subsequently, we have responded to the Agency’s request for additional information and we look forward to continuing to engage with them as part of our commitment to explore every opportunity to deliver zorevunersen to patients as quickly as possible.”

EMPEROR Study Details

Outside of major motor seizure frequency, the study will also assess several secondary outcomes that comprise change in behavior and cognition, clinical status, and health-related quality of life. In the study, eligible patients must have experienced seizure onset before 12 months of age, with no alternative identified etiology to explain their Dravet-like symptoms.²

For EMPEROR, genetic confirmation is also required, with patients needing a documented pathogenic, likely pathogenic, or variant of uncertain significance in the SCN1A gene. To qualify, patients must meet a minimum threshold of major motor seizures during a 6-week observation period and must have previously tried at least 2 seizure interventions without achieving adequate seizure control or discontinued them due to adverse events. Any ongoing maintenance antiseizure medications and other seizure-directed therapies, including cannabinoid-based products, must remain stable.

Key exclusions include SCN1A variants associated with gain-of-function, as well as the use of maintenance antiseizure medications that primarily act as sodium channel blockers, such as phenytoin, carbamazepine, or lamotrigine. Patients receiving neuromodulation therapies other than vagus nerve stimulation are also excluded. Additional criteria include clinical instability during baseline, such as the emergence of a new seizure type or the return of a previously resolved seizure type, as well as experiencing more than one seizure-related hospitalization during the baseline period.

Zorevunersen’s Early-Stage Data

Zorevunersen was initially evaluated in the phase 1/2 MONARCH (NCT00442295) and ADMIRAL studies, along with their open-label extension phases, SWALLOWTAIL and LONGWING. Across MONARCH and ADMIRAL, a total of 81 patients with Dravet syndrome were enrolled. MONARCH, conducted in the United States, included both single-ascending dose and multiple-ascending dose components, while the UK-based ADMIRAL study assessed repeated dosing of zorevunersen up to 70 mg.

Despite the refractory nature of the population studied, early results were notable. More than 85% of participants were taking at least 3 antiseizure medications at baseline, yet median seizure frequency remained high at 17 seizures per 28 days. Among patients who received 2 or 3 doses of 70 mg, median seizure reductions reached 85% at 3 months and 74% at 6 months.^3,4

Investigators also reported improvements that extended beyond seizure control, including gains in quality of life and functional outcomes. In the 70-mg single- and multiple-dose cohorts, European Quality of Life 5 Dimension Youth scores increased by 7.756, and both clinicians and caregivers noted favorable changes on the Clinical Global Impression of Change and Caregiver Global Impression of Change scales, respectively. In ADMIRAL, improvements were also seen across multiple Vineland-3 adaptive behavior subdomains, including receptive communication (5.778), personal skills (2.030), and gross motor function (3.517).

From a safety standpoint, zorevunersen was generally well tolerated at doses up to 70 mg. Treatment-related TEAEs were reported in 30% of treated patients, most commonly cerebrospinal fluid protein elevations and procedural vomiting. Grade 3 or higher TEAEs occurred in 13 patients (16%), and one participant experienced a fatal event consistent with presumed sudden unexpected death in epilepsy that investigators considered unrelated to treatment. Importantly, no adverse events led to study withdrawal.

Related Educational Content

In late-2025, NeurologyLive launched a multi-part Special Report featuring epilepsy experts Scott Perry, MD, and Joseph Sullivan, MD, outlining zorevunersen and its long-term outlook as a potential disease-modifying treatment for DS. In the final episode of the series pictured below, Sullivan described the extensive planning that went into structuring the EMPEROR trial, from dose selection and duration to endpoint timing. He explains how the trial balances the need for statistical power and ethical feasibility, using a sham-controlled design with defined primary and secondary endpoints. The study’s structure, he notes, is intended to capture both early seizure outcomes and longer-term functional benefits while maintaining scientific rigor and participant safety.

REFERENCES
1. Stoke Therapeutics Announces Updates to Timelines for the Completion of Enrollment and a Phase 3 Data Readout from the EMPEROR Study of Zorevunersen for the Treatment of Dravet Syndrome. News release. Stoke Therapeutics. January 11, 2026. Accessed January 12, 2026. https://investor.stoketherapeutics.com/news-releases/news-release-details/stoke-therapeutics-announces-updates-timelines-completion

2. Stoke Therapeutics announces alignment with global regulatory agencies and plans to initiate a phase 3 study of zorevunersen as potentially the first disease-modifying medicine for the treatment of Dravet syndrome. News release. Stoke Therapeutics. January 7, 2025. Accessed August 20, 2025. https://investor.stoketherapeutics.com/news-releases/news-release-details/stoke-therapeutics-announces-alignment-global-regulatory

3. Sullivan J, Cross HJ, Desurkar A, et al. Zorevunersen (STK-001) demonstrates potential for disease modification including reductions in seizures and improvements in cognition and behavior in children and adolescents with Dravet syndrome (DS). Presented at: 2024 American Epilepsy Society Annual Meeting; December 6-10, 2024; Los Angeles, CA.

4. Cross HJ, Laux L, Sullivan J, et al. MONARCH and ADMIRAL: open-label, phase 1/2a studies in USA and UK investigating safety, drug exposure, and clinical effect of zorevunersen (STK-001), an antisense oligonucleotide, in children and adolescents with Dravet syndrome. Presented at: European Epilepsy Congress. September 7-11; 2024.