Biogen, Stoke Therapeutics Launch Phase III Trial of Investigational Antisense Therapy for Dravet Syndrome

Author(s):

Key Takeaways

Zorevunersen, an investigational antisense oligonucleotide, is being evaluated in a global Phase III trial for Dravet syndrome.
The EMPEROR trial involves 150 children with Dravet syndrome, assessing efficacy, safety, and tolerability of zorevunersen.
Primary endpoint is the percent change in major motor seizure frequency, with secondary endpoints on cognitive and behavioral improvements.
Dravet syndrome is a severe genetic epilepsy with significant impact on patients and caregivers, highlighting the need for new treatments.

The global Phase III EMPEROR trial (NCT06872125) will evaluate the safety and efficacy of zorevunersen, a novel antisense oligonucleotide designed to reduce seizures and improve cognitive and behavioral outcomes in children with Dravet syndrome.

Image Credit: Adobe Stock Images/Magnimage

Topline Findings

First Patient Dosed: Biogen and Stoke Therapeutics initiate Phase III EMPEROR trial of zorevunersen for Dravet syndrome across multiple countries.
Trial Design Highlights: Double-blind, sham-controlled study enrolling approximately 150 children with SCN1A mutation, assessing seizure frequency and cognitive improvements.
Potential Breakthrough: Zorevunersen aims to be the first disease-modifying treatment addressing seizures, behavior, and cognition in Dravet syndrome patients.

Biogen and Stoke Therapeutics have announced dosing of the first patient in the global Phase III EMPEROR trial (NCT06872125) evaluating zorevunersen. The investigational antisense oligonucleotide has shown the potential to become the first disease-modifying treatment for Dravet syndrome. The trial is underway in the United States, United Kingdom, and Japan, with plans to expand into Europe.¹

How Did Zorevunersen Perform in Early Phase Trials for Dravet Syndrome?

“Our Phase I/II and open-label extension studies have provided a large dataset to support our understanding of zorevunersen and guide the EMPEROR study design, including dosing, duration and selection and powering of the endpoints,” said Barry Ticho, MD, PhD, chief medical officer, Stoke Therapeutics, in a press release. “Given the severity of this disease and the limitations of current treatments, the substantial and durable reductions in seizures and continuing improvements in cognition and behavior support our belief that zorevunersen may improve outcomes for patients with Dravet syndrome.”

EMPEROR Trial Design and Patient Population

The global, double-blind, sham-controlled EMPEROR trial will evaluate the efficacy, safety, and tolerability of zorevunersen in approximately 150 children aged two to under 18 years with Dravet syndrome and a confirmed variant in the SCN1A gene not associated with gain of function.
Patients will be randomly assigned in a 1:1 ratio to receive either zorevunersen via intrathecal administration or a sham comparator for a 52-week treatment period following an eight-week baseline period.
Patients receiving active treatment will be given two 70 mg loading doses on the first day and again at week eight, followed by two 45 mg maintenance doses at week 24 and week 40.
Throughout the trial, all patients will continue their standard-of-care medications.
Following the treatment period, eligible patients will have the opportunity to continue treatment as part of an open-label extension study.

Endpoints and Clinical Significance

The primary endpoint of the trial is percent change from baseline in major motor seizure frequency at week 28 in patients receiving zorevunersen compared to sham.
Key secondary endpoints include the lasting impact on the frequency of major motor seizures along with enhancements in behavior and cognitive functions, assessed through Vineland-3 subscales such as expressive and receptive communication, social interactions, coping abilities, and daily living skills.^1,2

“The initiation of the EMPEROR study is a critical milestone in zorevunersen's development,” said Katherine Dawson, MD, head, therapeutics development unit, Biogen, in the press release. “Despite treatment with available anti-seizure medicines, no approved medications currently address the underlying cognitive and behavioral aspects of this rare, genetic disease. Together with Stoke, we look forward to working in collaboration with the hope of bringing forward zorevunersen as the first disease-modifying treatment option, if approved, for Dravet syndrome.”

Background on Dravet Syndrome

According to Orphanet, the estimated prevalence of Dravet syndrome at birth is one in 30,000 people, however, the exact prevalence is unknown. The onset of the first seizure is usually between five and eight months of age. An estimated 85% of all cases are a result of a mutation or deletion in the SCN1A gene.³

“Dravet syndrome is one of the most well studied genetic epilepsies so we know the significant and life-altering effects it can have on patients and their caregivers,” said Joseph Sullivan, MD, FAES, EMPEROR trial principal investigator, professor of neurology and pediatrics, director, pediatric epilepsy center of excellence, University of California San Francisco, in the press release. “Providing additional relief from seizures remains an important clinical outcome, but the potential to address the underlying genetic cause to also address neurodevelopmental symptoms signals a fundamentally new way of treating the disease. The urgent need for treatments is evident in the high degree of interest in the EMPEROR study.”

References

Biogen and Stoke Therapeutics Announce First Patient Dosed in Phase 3 EMPEROR Study of Zorevunersen, a Potential Disease-Modifying Treatment for Dravet Syndrome. Biogen. August 11, 2025. Accessed August 11, 2025. https://investors.biogen.com/news-releases/news-release-details/biogen-and-stoke-therapeutics-announce-first-patient-dosed-phase
A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients With Dravet Syndrome. Clinicaltrials.gov. Accessed August 11, 2025. https://clinicaltrials.gov/study/NCT06872125?term=EMPEROR&aggFilters=phase:3&rank=1
Dravet syndrome. Orphanet. Accessed August 11, 2025. https://www.orpha.net/en/disease/detail/33069#:~:text=MedDRA:%2010073677,1/15%2C000%2D40%2C000).

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