Mechanism Behind Novel STK-001 as Disease-Modifying Treatment for Dravet Syndrome: Barry Ticho, MD, PhD

WATCH TIME: 3 minutes

"Our medicine can increase protein levels inside cells—a rare feat—and early safety data suggests it is well-tolerated, offering hope for children with this devastating disease."

Developing an effective treatment for Dravet syndrome can be difficult, due to the fact that these patients experience a number of complications in addition to seizures, which often remain uncontrolled. More recently, the FDA granted breakthrough therapy designation to Stoke Therapeutics investigational antisense agent STK-001, otherwise known as zorevunersen, as a potential treatment for the disease. Currently, more than 600 doses of the medication have been administered to patients, with some currently on the drug for more than 3 years.

The belief is that STK-001 can be more than just a typical therapy for DS, but instead a disease-modifying one that improves all aspects of the disease. To date, the agent has shown promising results in the phase 1/2 MONARCH (NCT04740476) and ADMIRAL (NCT04442295) studies, as well as their extensions, SWALLOWTAIL and LONGWING. Data from these studies presented at the 15^th European Epilepsy Congress and the 2024 American Epilepsy Society (AES) Annual Meeting, highlighted the treatment’s impacts on seizure control and in other areas like cognition, behavior, quality of life, and overall clinical status.

During AES 2024, NeurologyLive® sat down with Barry Ticho, MD, PhD, chief medical officer at Stoke, to better understand more about the mechanism behind the agent, which leverages the company’s proprietary TANGO platform. He spoke about how this therapy differs from traditional RNA medicines that reduce protein levels, as well as some of the early promising safety findings seen. Furthermore, when discussing safety, Ticho talked about the manageable adverse events like elevated cerebrospinal fluid protein levels, a class effect with no clinical consequences.

Click here for more AES 2024 coverage.

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
3. Brunklaus A, Perry MS, Sullivan J, et al. SWALLOWTAIL and LONGWING Open-label Extension Studies for Children and Adolescents with Dravet Syndrome who Previously Participated in a Study of Antisense Oligonucleotide Zorevunersen (STK-001). Presented at: 2024 European Epilepsy Congress. POSTER P875