Barry S. Ticho, MD, PhD, Chief Medical Officer at Stoke Therapeutics, discusses the phase 1/2a MONARCH study, which is evaluating STK-001 in patients with Dravet syndrome.

As Dr. Ticho explains, Dravet syndrome is a rare neurological condition that usually appears during the first year of life as frequent febrile seizures. As the condition progresses, other types of seizures typically occur, including myoclonus and status epilepticus. Moderate to severe cognitive impairment is also common. Most cases of Dravet syndrome occur due to a mutation of the SCN1A gene. The SCN1A gene codes for the protein NaV1.1. With only 1 functional SCN1A gene, people with Dravet syndrome produce less of the NaV1.1 protein. NaV1.1 is an important protein for the nerves in the brain to work properly. Low levels of NaV1.1 in the brain can lead to seizures and other symptoms of Dravet syndrome.

As Dr. Ticho explains, Stoke Therapeutics is currently evaluating the safety and tolerability of single and multiple ascending doses of STK-001, which has the potential to be the first disease-modifying therapy to target the underlying cause of Dravet syndrome. STK-001 is an antisense oligonucleotide that is intended to increase the level of productive SCN1A mRNA and thereby increase the expression of theNav1.1 protein.

STK-001 is being evaluated in children and adolescents with Dravet syndrome caused by a SCN1A mutation in the phase 1/2a MONARCH study. Increasing levels of single or three doses will be given to each participant in this open-label study. In December 2021, initial data from the MONARCH study were presented at the American Epilepsy Society 2021 Meeting. This data demonstrated the following:

  • Single doses of STK-001 up to 30mg, and three 20mg doses of STK-001 given every four weeks, appeared to be well tolerated with no safety concerns related to the study drug. 
  • The most common treatment-emergent adverse events (TEAE) were headache, vomiting, seizure, irritability, and back pain. 
  • 70.6% (12/17) of patients treated with single doses (10mg, 20mg, 30mg) or multiple doses (20mg) of STK-001 experienced a reduction from baseline in convulsive seizure frequency measured from Day 29 to Day 84 after receiving their first dose of STK-001. 
  • All patients ages 2-12 (n=7) experienced a reduction from baseline in convulsive seizure frequency measured from Day 29 to Day 84. Reductions in seizure frequency were also observed among patients ages 13-18. 
  • Across all cohorts, median reductions of 17% to 37% from baseline in convulsive seizure frequency from Day 29 to Day 84 were observed.

Change in seizure frequency, overall clinical status, and quality of life will be measured as secondary endpoints in this open-label study.

Stoke recently announced positive interim data from the ongoing Phase 1/2a MONARCH and ADMIRAL clinical studies of STK-001.

To learn more about Dravet syndrome and other rare neurological disorders, visit