Clinical Program and Next Steps for Zorevunersen as Potential Disease-Modifying Treatment for Dravet: Barry Ticho, MD, PhD

WATCH TIME: 5 minutes

"This will be the first potential disease-modifying therapy brought into the clinic for any epilepsy, offering families and children a completely new lifestyle."

Zorevunersen (Stoke Therapeutics), also known as STK-001, is an investigational antisense oligonucleotide in development as a disease-modifying treatment for patients with Dravet syndrome (DS), a rare epileptic disorder. Across several completed phase 1 studies and their extensions, the agent has demonstrated an impact on patients’ seizure control, as well as addressing the neurodevelopmental issues associated with DS, including the ability to communicate and the ability to achieve a certain level of independence that is not seen with today’s standard of care.

In the days leading up to the 2024 American Epilepsy Society (AES) Annual Meeting, held December 6-10 in Los Angeles, California, the FDA granted breakthrough therapy designation to zorevunersen, signifying its promise and allowing for expedited development and review. During the meeting, Stoke presented several analyses of zorevunersen, including new data on a small subset of patients who initially received higher, 70-mg doses of the drug followed by an open-label extension where they received at least 2 doses of 45 mg.

During the meeting, NeurologyLive® sat down with Barry Ticho, MD, PhD, chief medical officer at Stoke, to discuss the impact of the data, as well as the FDA’s decision to grant breakthrough therapy designation to zorevunersen. In the discussion, Ticho also spoke on how zorevunersen targets the underlying cause of the disease, offering benefits across multiple domains, including cognition, behavior, and motor function. In addition, he spoke on the potential phase 3 study, which will serve as a registrational trial for future regulatory submission. Furthermore, he spoke on how the phase 3 trial will aim to confirm the therapy’s effects, as well as the potential impact the treatment could bring to patients if the study results are successful.

Click here for more coverage of AES 2024.

REFERENCES
1. Stoke Therapeutics Receives FDA Breakthrough Therapy Designation for Zorevunersen for the Treatment of Dravet Syndrome. News release. Stoke Therapeutics. December 4, 2024. Accessed December 9, 2024. https://investor.stoketherapeutics.com/news-releases/news-release-details/stoke-therapeutics-receives-fda-breakthrough-therapy-designation/
2. 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: EEC