FDA Lifts Part of Partial Hold on Stoke’s Dravet Drug Trial to Allow Administration of Higher Single Dose

FDA Lifts Part of Partial Hold on Stoke’s Dravet Drug Trial to Allow Administration of Higher Single Dose

Rare Daily Staff

Stoke Therapeutics said that the U.S. Food and Drug Administration has lifted a part of the partial hold and will allow the administration of a higher single dose of STK-001 (70 mg) in its ongoing phase 1/2a MONARCH study of children and adolescents with Dravet syndrome.

This new 70mg single dose cohort in MONARCH will complement the ongoing evaluation of multiple doses of 70mg in the ADMIRAL study.

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures beginning within the first year of life. Complications of the disease often contribute to poor quality of life for patients and their caregivers. Despite available anti-seizure medicines, seizures are not adequately controlled for more than 90 percent of patients. STK-001 is a proprietary antisense oligonucleotide (ASO) being developed by Stoke as the first potential new medicine to address the genetic cause of Dravet syndrome.

“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,” said Barry Ticho, chief medical officer of Stoke Therapeutics. “We expect data from this new dose cohort to provide information about the potential effects and durability of a single dose of 70mg. We look forward to dosing the first patient in the coming weeks and to be able to include preliminary findings in our anticipated data readout in the second half of 2023.”

The FDA placed a partial hold on Stoke’s trial three years ago to limit the dose level, starting at 20 mg, which the FDA has steadily allowed to increase based on data from the current dose level.

Stoke anticipates reporting data from patients treated with multiple 45mg doses of STK-001 in mid-2023. Data from patients treated with 70 mg of STK-001 in MONARCH (single dose) and ADMIRAL (multiple doses) are anticipated in the second half of 2023. The company expects to complete the phase 1/2a studies of STK-001 in 2023 in order to initiate a phase 3 program in 2024. The MONARCH study remains on partial clinical hold for multiple doses of STK-001 above 45 mg.

The MONARCH study is a phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study are to assess the safety and tolerability of STK-001, as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective is to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life, as secondary endpoints.

Patients who participated in the MONARCH study and meet study entry criteria are eligible to continue treatment in SWALLOWTAIL, an open-label extension study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001. Enrollment and dosing in SWALLOWTAIL are underway.

The ADMIRAL study is a phase 1/2a open-label study of children and adolescents ages 2 to less than 18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study are to assess the safety and tolerability of multiple doses of STK-001, as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective is to assess the effect of multiple doses of STK-001 as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Stoke also intends to measure non-seizure aspects of the disease, such as overall clinical status and quality of life, as secondary endpoints.

Patients who participated in the ADMIRAL study and meet study entry criteria are eligible to continue treatment in LONGWING, an open-label extension study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001.

Photo: Barry Ticho, chief medical officer of Stoke Therapeutics