FDA allows higher dose of investigational drug in study of children with Dravet syndrome

Key takeaways:

• Stoke Therapeutics may administer a 70 mg single dose of STK-001 to children and adolescents with Dravet syndrome in its phase 1/2a MONARCH study.
• Data from the study is anticipated by the second half of 2023.

Stoke Therapeutics Inc. announced the FDA will allow administration of a higher single dose of its investigational drug STK-001 in its ongoing phase 1/2a MONARCH study of children and adolescents with Dravet syndrome.

According to a release from Stoke, the new 70 mg single dose cohort in the MONARCH study will complement the evaluation of multiple doses of 70 mg in the ongoing ADMIRAL study. With no currently approved disease-modifying therapies for Dravet syndrome, the novel antisense oligonucleotide STK-001 has the potential to become the first to address the genetic cause of Dravet syndrome, the company stated.

“There is an urgent need for a disease modifying approach to treat Dravet syndrome, a devastating disease with effects that go beyond seizures and impact quality of life for patients and their families,” Barry Ticho, MD, PhD, chief medical officer at Stoke Therapeutics, said in the release. “We expect data from this new dose cohort to provide information about the potential effects and durability of a single dose of 70 mg.”

MONARCH is a phase 1/2a open-label study of children and adolescents in the United States, aged 2 to 18 years, who have an established diagnosis of Dravet syndrome and evidence of a genetic mutation in the SCN1A gene. The ADMIRAL is a similar study in the United Kingdom of children and adolescents aged 2 years to younger than 18 years, with Dravet syndrome and evidence of a genetic mutation in SCN1A.

The primary objectives for both studies, according to the release, are to assess the safety and tolerability of STK-001, as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. Secondary endpoints in both studies include measures of quality of life.

According to Stoke, data from individuals treated with multiple 45 mg doses of STK-001 are anticipated by the middle of 2023, while data from those given a single 70 mg dose in MONARCH and multiple 70 mg doses in ADMIRAL are anticipated in the latter half of 2023. With completion of all phase 1/2a studies expected in 2023, a phase 3 program will begin in 2024.