Positive data reported from clinical trials of novel therapeutic for Dravet syndrome

Key takeaways:

• An analysis of phase 1/2a studies and an open-label extension for STK-001 showed correlation between dosage and seizure reduction.
• Results are expected to guide optimal dosing for a pending phase 3 study.

Stoke Therapeutics Inc. has announced new positive data regarding its proprietary antisense oligonucleotide therapeutic to treat Dravet syndrome.

Data from the study were to be presented at the International Epilepsy Congress from Sept. 2 to Sept. 6, in Dublin.

According to a release from Stoke, results from ongoing phase 1/2a studies (MONARCH & ADMIRAL), the SWALLOWTAIL open-label extension study, as well as pharmacokinetic analysis of the clinical trials, showed correlations between higher drug exposure and greater reductions in seizure frequency.

Interim analyses of both MONARCH and ADMIRAL showed that single and multiple doses of STK-001 up to 70 mg were generally well tolerated, while those given two or three initial doses at 70 mg experienced significant and sustained median reductions in convulsive seizure frequency of 80% (n = 6) at 3 months and 89% (n = 3) at 6 months following last dose compared with baseline, per the release.

Further, Stoke reported in the release that safety findings in SWALLOWTAIL were consistent with those from MONARCH and ADMIRAL, excepting greater incidence of CSF protein elevation; however, durable reductions in convulsive seizure frequency were observed throughout the course of treatment. Data from the open-label extension also indicated substantial improvements in cognition and behavior from baseline to 12 months with continued STK-001 dosing.

Additionally, per the release, pharmacokinetic analysis yielded a positive relationship between STK-001 brain exposure and convulsive seizure frequency in 61 participants, with exposure-seizure relationship showing a significant negative trend based on simulated brain Cavg (R = -0.23, P < 0.001). These results are likely to identify an optimal dose for a planned phase 3 study of the novel therapeutic, the company said.

“Our clinical findings to date show that patients treated with STK-001 experienced substantial and sustained reductions in seizures and importantly,

improvements in cognition and behavior,” Barry Ticho, MD, PhD, chief medical officer of Stoke Therapeutics, said in the release. “The new data from our pharmacokinetic model provide additional confidence in the observed effects of STK-001.”

Stoke is expected to release further data regarding dose and dose regimen by the first quarter of 2024, along with updated plans for a phase 3 clinical trial.