BEDFORD, Mass., and CAMBRIDGE, Mass. — Stoke Therapeutics and Biogen have begun dosing patients in the global Phase 3 EMPEROR study of zorevunersen, an experimental antisense oligonucleotide that could become the first disease-modifying treatment for Dravet syndrome.
The rare genetic disorder, most often caused by mutations in the SCN1A gene, leads to frequent, treatment-resistant seizures along with developmental and behavioral impairments. Current therapies focus on controlling seizures but do not address the underlying cause.
“Our Phase 1/2 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, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “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.”
The study will enroll children and adolescents aged 2 to 18 with a confirmed SCN1A variant not associated with gain of function. After an eight-week baseline period, participants will be randomized to receive either zorevunersen or a sham procedure for 52 weeks, alongside standard care medicines. Patients in the active arm will get two 70 mg loading doses followed by two 45 mg maintenance doses.
Primary goals include measuring changes in major motor seizure frequency at 28 weeks. Secondary measures will assess seizure frequency at 52 weeks, as well as changes in behavior and cognition using Vineland-3 subdomains such as expressive communication, coping skills, and interpersonal relationships.
“The initiation of the EMPEROR study is a critical milestone in zorevunersen’s development,” said Katherine Dawson, M.D., head of Biogen’s Therapeutics Development Unit. “Despite treatment with available anti-seizure medicines, no approved medications currently address the underlying cognitive and behavioral aspects of this rare, genetic disease.”
Joseph Sullivan, M.D., principal investigator and professor of neurology and pediatrics at the University of California, San Francisco, said the trial represents “a fundamentally new way of treating the disease.” He noted that while seizure reduction remains important, the potential to address neurodevelopmental symptoms by targeting the genetic cause has generated strong interest from families.
Patients who complete the trial will have the option to continue treatment in an open-label extension study.
