Stoke Therapeutics: A New Era in Dravet Syndrome Treatment
Tuesday, Jan 7, 2025 7:16 am ET
CGTX --
STOK --
Stoke Therapeutics, a biotechnology company dedicated to restoring protein expression through RNA medicine, has announced a significant milestone in its quest to develop a disease-modifying therapy for Dravet syndrome. The company has aligned with global regulatory agencies, including the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), to initiate a Phase 3 study of its investigational medicine, zorevunersen. This collaboration has expedited the timeline for the study, with plans to begin in mid-2025.

Dravet syndrome is a severe and progressive genetic epilepsy, characterized by frequent, prolonged seizures and significant neurodevelopmental issues. Current treatments primarily focus on seizure control, but they do not address the broader impact of the condition on patients' lives. Stoke Therapeutics' zorevunersen, an antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. The drug is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene, thereby reducing both occurrence of seizures and significant non-seizure comorbidities.
The pivotal Phase 3 study, EMPEROR, will be a global, randomized, double-blind, sham-controlled trial. It will enroll approximately 150 patients with Dravet syndrome between the ages of 2 to <18 years of age. The primary endpoint will be reduction in major motor seizure frequency, while key secondary endpoints will include improvements in cognition and behavior as measured primarily by Vineland-3. This comprehensive evaluation will provide a more holistic understanding of zorevunersen's potential as a disease-modifying therapy, potentially ushering in a new era in Dravet syndrome treatment.
The alignment with global regulatory agencies has not only expedited the timeline for the Phase 3 study but has also streamlined the development process, making the study more feasible and efficient. The regulatory agencies' support and collaboration have been crucial in finalizing the study protocol, which aims to evaluate two loading doses of 70mg followed by two maintenance doses of 45mg over 52-weeks compared to sham in children and adolescents ages 2 to <18 with Dravet syndrome.
The potential of zorevunersen as a disease-modifying therapy for Dravet syndrome aligns well with an investment philosophy focused on stable, predictable, and lucrative investments. The drug has shown substantial and durable reductions in seizure frequency, with an 87% median reduction in convulsive seizure frequency at month eight. Additionally, it has demonstrated improvements in multiple measures of cognition and behavior, suggesting a broad impact on the disease. The drug has been generally well-tolerated, with over 600 doses administered to patients across multiple studies. The alignment with global regulatory agencies for the EMPEROR Phase 3 study further supports the drug's potential, as does the FDA's Breakthrough Therapy Designation. These factors indicate a stable and predictable development path, with the potential for significant returns on investment.
In conclusion, Stoke Therapeutics' announcement of 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 is a significant milestone in the quest for a more comprehensive and effective treatment for this severe and progressive genetic epilepsy. The potential of zorevunersen aligns well with an investment philosophy focused on stable, predictable, and lucrative investments, making it an exciting opportunity to watch as the study progresses.