Promising Results Reported for Antisense Oligonucleotide STK-001 as Potential Treatment for Dravet Syndrome

Analysis of interim results from the ongoing SWALLOWTAIL (NCT04740476) and LONGWING (2021-005626-14) open label extension (OLE) studies of antisense oligonucleotide (ASO) STK-001 (Stoke Therapeutics, Bedford, MA) for the treatment of individuals with Dravet syndrome (DS) revealed sustained reduction in seizure frequency, improvements in cognitive and behavior outcomes, and a favorable safety profile. The study results were presented at the 2023 American Epilepsy Society (AES) Annual Meeting.

SWALLOWTAIL and LONGWING are ongoing multicenter OLE studies consisting of 51 participants who completed either the STK-001 phase 1/2a MONARCH (NCT04442295) or ADMIRAL (2020-006016-24) study. MONARCH and ADMIRAL study participants received up to 7 STK-001 doses (10-45 mg/dose) delivered every 4 months. SWALLOWTAIL and LONGWING OLE participants are currently receiving 30 mg/dose and LONGWING participants are receiving 45 mg/dose via intrathecal injection. Interim results have demonstrated the following:

• Multiple doses of STK-001 have been generally well-tolerated in SWALLOWTAIL and LONGWING participants. The only treatment-emergent adverse event (TEAE) related to the study drug in >1 patient was an increase in CSF protein reported in 24.1% of participants.
• A sustained reduction in convulsive seizure frequency in SWALLOWTAIL participants (LONGWING data not yet available)
• Improvements in measures of cognition and behavior assessed by the Vineland Adaptive Behavior Scales Third Edition (VABS-III) and Behavior Rating Inventory of Executive Function Preschool (BRIEF-P) in SWALLOWTAIL participants (LONGWING data not yet available)

Around 85% of DS cases are caused by heterozygous loss-of-function mutations in the SCN1A gene, which encodes the brain voltage-gated sodium channel type 1 α subunit (Nav1.1) protein. STK-001 is an investigational ASO with the potential to reduce seizure frequency and non-seizure comorbidities through the upregulation of Na v1.1.

Joseph Sullivan, MD, study author and director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco notes “One of the most exciting things we are seeing is the early sign that, for the first time, we may have a therapy that can address the syndrome in addition to the seizures.”

This study is supported by Stoke Therapeutics. According to the company, additional data from the SWALLOWTAIL and LONGWING trials will be released in the first quarter of 2024.