STK-001 as a Potential First Disease-Modifying Treatment for Dravet Syndrome

Stoke Therapeutics, a company at the forefront of RNA-based medicine, has unveiled significant findings from its Phase 1/2a clinical trials and open-label extension studies involving STK-001, a treatment for Dravet syndrome. The data indicated substantial and sustained reductions in convulsive seizure frequency, a key indicator for the syndrome, even when administered alongside existing anti-seizure medications. Notably, patients treated with 70mg doses of STK-001 exhibited a median reduction of 85% at three months and 74% at six months post-treatment.

The open-label extension studies further highlighted the durability of seizure reduction and reported clinically meaningful improvements in cognitive and behavioral measures over a 12-month period with continued dosing. STK-001 demonstrated a favorable safety profile, being generally well-tolerated by the patients throughout the studies.

The U.S. Food and Drug Administration (FDA) has granted Stoke Therapeutics clearance to administer three doses of 70mg of STK-001, followed by a sustained dosage of 45mg. Armed with this regulatory endorsement and the promising study outcomes, Stoke intends to confer with regulatory bodies to outline a registrational study design.

Dravet syndrome is a severe genetic epilepsy with atypically high and treatment-resistant seizures, often leading to intellectual disabilities and developmental delays. Currently, no disease-modifying therapies exist for this condition. STK-001, an antisense oligonucleotide, is designed to upregulate the expression of the NaV1.1 protein, leveraging the non-mutant copy of the SCN1A gene to normalize protein levels and mitigate seizure occurrences and associated comorbidities.

The clinical trials, MONARCH and ADMIRAL, were open-label Phase 1/2a studies that focused on the safety, tolerability, and pharmacokinetics of STK-001. Following these, eligible patients proceeded to the SWALLOWTAIL and LONGWING open-label extension studies to assess long-term safety, tolerability, and effects on convulsive seizure frequency, behavior, cognition, and quality of life.

The BUTTERFLY observational study, a separate initiative, monitored the natural progression of Dravet syndrome in patients receiving standard care. The findings from BUTTERFLY underscored the lack of significant improvement in convulsive seizure frequency and cognitive and behavioral development in patients, highlighting the urgent need for effective treatments.

Stoke Therapeutics, headquartered in Bedford, Massachusetts, is committed to pioneering RNA-based therapeutics to address severe diseases by modulating protein expression. The company's innovative TANGO platform aims to selectively restore protein levels, with STK-001 being the first compound in clinical development for Dravet syndrome. Stoke is also advancing STK-002 for the treatment of autosomal dominant optic atrophy (ADOA), marking its expansion into other central nervous system and eye-related diseases.