Positive data reported in phase 1/2a studies of therapeutic for pediatric Dravet syndrome

Key takeaways:

• STK-001 was investigated in a pair of phase 1/2a studies for Dravet syndrome in children and adolescents.
• The study found a significant reduction in seizure frequency at 3 months across all three cohorts.

A biotechnology company has announced positive safety and efficacy data from two ongoing phase 1/2a studies as well as an open-label extension study of STK-001 to treat younger individuals with Dravet syndrome.

According to a release from Stoke Therapeutics, STK-001 is a proprietary antisense oligonucleotide currently under investigation in the MONARCH and ADMIRAL clinical trials as well as the SWALLOWTAIL OLE trial.

The primary objectives of both studies — MONARCH in the United States and ADMIRAL in the United Kingdom — are safety, tolerability and pharmacokinetic assessments of the drug, with a secondary objective of assessing its efficacy as adjunctive antiepileptic treatment.

In each clinical trial, 45 children and adolescents were treated with multiple doses (30 mg, 45 mg, 70 mg) of STK-001. Analysis of both revealed the greatest reduction in convulsive seizure frequency in the 11 individuals administered either two or three doses of 70 mg in the ADMIRAL study. As early as 3 months after last dose across all cohorts, there was a significant median reduction from baseline in seizure frequency, which was maintained up to 6 months after the final dose.

Also per the release, data from a mixed model repeated measures analysis revealed significant improvement from baseline through 12 months in expressive and receptive communication as measured by the Vineland Adaptive Behavior Scale (VABS-III); gross motor skills as measured by VABS-III; executive function as measured by the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) and Global Impression of Change scores logged by both clinicians and caregivers.

The company further said STK-001 was generally well-tolerated among participants administered single and multiple doses of 10 mg to 70 mg, and there were no recorded drug-related discontinuations. However, 32% of enrollees experienced a treatment-emergent adverse event related to the drug, the most common being CSF protein elevations, vomiting and irritability, and 20% of patients logged a treatment-emergent serious adverse event, although 14 of the 15 adverse events were not considered related to the therapeutic.

“Together these data support the potential for STK-001 to address the underlying cause of Dravet syndrome by treating both seizures and the cognitive and behavioral issues that make this disease so complex and devastating,” Stoke Therapeutics CEO Edward M. Kaye, MD, said in the release.

Kaye additionally said the ongoing studies are expected to conclude by the end of 2023, with data sharing expected in the first quarter of 2024.