– Data from multiple ongoing clinical studies of STK-001 show reductions in convulsive seizure frequency and improvements in cognition and behavior in children and adolescents with Dravet syndrome –
– Data support the potential for STK-001 to be the first disease-modifying treatment for Dravet syndrome –
– New pharmacokinetic (PK) modeling of clinical data from ongoing studies demonstrate that higher STK-001 drug exposures in brain correlate with greater reductions in seizure frequency –
DUBLIN--(BUSINESS WIRE)-- Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines, today announced highlights from presentations related to the ongoing clinical development of STK-001, the first potential new medicine to treat the underlying cause of Dravet syndrome. Four posters from the Company’s work in Dravet syndrome are being presented at the International Epilepsy Congress (IEC) 2023, September 2-6, in Dublin, Ireland. Data from the recently announced analysis of results from the ongoing Phase 1/2a studies (MONARCH & ADMIRAL) and the SWALLOWTAIL open-label extension study are being presented in a scientific forum for the first time. In addition, a new pharmacokinetic (PK) analysis of 61 patients treated in STK-001 clinical trials is being presented for the first time, and demonstrates a correlation between higher STK-001 drug exposure in brain and greater reductions in seizure frequency over time.
Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures beginning within the first year of life. The disease is classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease.
“The data from ongoing studies of STK-001 provide the first evidence of a disease modifying medicine for Dravet syndrome,” said Helen Cross, MB ChB, Ph.D., Professor, The Prince of Wales’s Chair of Childhood Epilepsy and Director of University College London Great Ormond Street Institute of Child Health, Honorary Consultant in Paediatric Neurology, and the ADMIRAL study lead investigator. “The primary goal of these studies is to assess safety and tolerability as well as to inform dose selection for future studies. Importantly, within these data we can now see a differentiated pattern of response emerging among the 11 patients treated with an initial two or three doses of 70mg. Additionally, data from the open-label extension study that is evaluating ongoing dosing at lower levels showed, for the first time, improvements in multiple measures of cognition and behavior among patients who have been highly refractory to standard anti-seizure medicines.”
The potential of STK-001, a proprietary antisense oligonucleotide (ASO), to be the first disease-modifying medicine for Dravet syndrome is supported by multiple presentations of clinical and other data at IEC.
- MONARCH and ADMIRAL Interim Analyses: Single and multiple doses of STK-001 up to 70mg were generally well tolerated. Patients treated with 2 or 3 initial doses of 70mg experienced substantial and sustained reductions in convulsive seizure frequency with median reductions of 80% (n=6) at 3 months and 89% (n=3) at 6 months after last dose, compared to baseline.
- SWALLOWTAIL open label extension (OLE): Safety findings among patients, who are continuing to be dosed with STK-001, were consistent with the findings from MONARCH and ADMIRAL with the exception of a greater incidence of CSF protein elevation. Durable reductions in convulsive seizure frequency were observed throughout the course of treatment in SWALLOWTAIL. Additionally, data indicated substantial improvements from baseline through 12 months of continued STK-001 dosing in multiple assessments of cognition and behavior.
- BUTTERFLY (natural history study): Small but significant improvements in receptive communication were observed at Month 12; however, little to no change was observed across other measures of cognition and behavior. Data from this study will inform future Dravet syndrome studies.
- PK Model for STK-001: A relationship between STK-001 brain exposure and convulsive seizure frequency was evaluated based on patients treated in the two ongoing Phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL OLE study in children and adolescents with Dravet syndrome. The exposure-seizure relationship showed a significant negative trend based on simulated brain Cavg (R=-0.23, P