Stoke Therapeutics Announces Phase 3 Study Plans for Zorevunersen in Dravet Syndrome
Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company focused on RNA medicine to restore protein expression, announced today that it has finalized its Phase 3 EMPEROR study design for zorevunersen, a potentially disease-modifying treatment for Dravet syndrome. The company achieved alignment with global regulatory agencies, including the FDA, EMA, and PMDA, following successful discussions, ensuring that the study will move forward as planned.
The EMPEROR study will evaluate zorevunersen’s efficacy in children and adolescents ages 2 to under 18 with Dravet syndrome. The proposed treatment regimen involves two loading doses of 70mg followed by two maintenance doses of 45mg over 52 weeks, compared to a sham treatment. The primary endpoint of the study will focus on the reduction in major motor seizure frequency, a core symptom of Dravet syndrome. Secondary endpoints will assess improvements in cognition and behavior, with a key measure being the Vineland-3, a comprehensive assessment tool for behavioral development. The Phase 3 study is slated to begin in mid-2025.
Edward M. Kaye, M.D., CEO of Stoke Therapeutics, expressed enthusiasm about the alignment, stating, “The global support for our Phase 3 study design brings us closer to our goal of offering the first disease-modifying medicine for Dravet syndrome.” He noted that the overwhelming support from clinicians, patient groups, and regulatory authorities highlights a shared belief that current treatments are inadequate. The Stoke is confident that data from earlier studies, which showed substantial and sustained reductions in seizure frequency and improvements in cognition and behavior with a similar dosing regimen, will lead to further advances.
Dr. Kelly Knupp, M.D., MSCS, Professor of Pediatrics and Neurology at the University of Colorado, emphasized the significance of the trial design. She remarked, “What families and clinicians truly want are therapies that go beyond seizure reduction to address the neurodevelopmental issues associated with Dravet syndrome. Zorevunersen is the first Phase 3 study to examine the effects of a disease-modifying drug on seizures and neurodevelopment, which could usher in a new era of treatment for Dravet syndrome.”
Zorevunersen has been granted FDA Breakthrough Therapy Designation, a designation aimed at expediting the development and review of drugs for serious conditions. This designation underscores the promising clinical data suggesting that zorevunersen may offer substantial improvements over existing therapies for Dravet syndrome.
Supporting the decision to move forward with the EMPEROR study, Stoke Therapeutics has shared promising clinical data from earlier phases. In the Phase 1/2a study, patients who received two or three doses of 70mg of zorevunersen saw an 87% median reduction in convulsive seizure frequency by month eight, which continued even four months after the second 45mg dose. Moreover, patients showed significant improvements in multiple cognitive and behavioral measures, assessed using the Vineland-3, throughout a two-year treatment period. These findings are particularly notable because the patients were already on the best available anti-seizure medications, underscoring the potential of zorevunersen to offer substantial benefits.
Zorevunersen has been well-tolerated across multiple studies. More than 600 doses have been administered to patients, with some remaining on the treatment for over three years without serious adverse events.
The EMPEROR pivotal Phase 3 trial will be a global, randomized, double-blind, sham-controlled study, enrolling approximately 150 children with Dravet syndrome, aged 2 to under 18, and confirmed to have a variant in the SCN1A gene that is not associated with a gain of function. The study will assess multiple endpoints, including seizure reduction, cognitive and behavioral improvements, and safety.
The trial will be conducted in the US, UK, EU, and Japan, and is set to run for 60 weeks, including an 8-week baseline period followed by a 52-week treatment phase. Data from the Phase 3 study are expected by the end of 2027, with an open-label extension study for eligible patients.
Through this initiative, Stoke Therapeutics aims to address the significant unmet medical need in Dravet syndrome, which severely impacts the quality of life for both patients and their families. The Stoke’s focus on RNA medicine and zorevunersen’s potential to modify the course of Dravet syndrome represents an important step forward in providing patients with a treatment option that goes beyond seizure control to improve their overall developmental and cognitive outcomes.
Stoke’s commitment to advancing zorevunersen is part of its broader goal to revolutionize the treatment landscape for severe genetic disorders, and the EMPEROR study marks a critical milestone in bringing this novel therapy to market.
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