US biotech company Stoke Therapeutics has secured orphan drug designation for its lead product candidate – STK-001 from the US Food and Drug Administration (FDA) for the treatment for Dravet syndrome.

Considered to be a severe and progressive genetic epilepsy, Dravet syndrome is characterized by frequent, prolonged and refractory seizures that start within the first year of life.

The effects of Dravet syndrome are beyond seizures and mostly include cognitive regression or developmental stagnation, ataxia, speech impairment, and sleep disturbances. When compared with people with general epilepsy population, those having Dravet syndrome have high chances of sudden unexpected death in epilepsy or SUDEP.

Nearly 85% of Dravet syndrome cases are due to spontaneous, heterozygous loss of function mutations in the SCN1A gene, which encodes the voltage-gated sodium channel type 1 alpha subunit (NaV1.1). Till date, available Dravet syndrome treatments do not address the mutation, which is the underlying cause of the disease.

According to Stoke Therapeutics, STK-001, which is an antisense oligonucleotide, can potentially become the first disease-modifying therapy to address Dravet syndrome’s underlying genetic cause.

STK-001 has been engineered to upregulate NaV1.1 protein expression from the non-mutant copy of the SCN1A gene for restoring physiological NaV1.1 levels, thereby bringing down occurrence of seizures and significant non-seizure comorbidities. Stoke Therapeutics has extracted preclinical data which shows proof-of-mechanism for STK-001.

Barry S. Ticho – Chief Medical Officer of Stoke Therapeutics, commenting on the STK-001 orphan drug designation from the FDA, said: “The need for a medicine that will treat the underlying cause of Dravet syndrome is clear to anyone who has seen the devastating effects of the disease, and the significant impact it has on patients and their families.

“Our goal with STK-001 is to slow or even stop disease progression by treating the underlying cause of Dravet syndrome. STK-001 is designed to selectively upregulate one allele of the SCN1A gene to restore the protein expression to near-normal levels.

“We are on track to submit our investigational new drug application for STK-001 to the FDA in early 2020 and to begin a Phase 1/2 clinical study in the first half of the year.”

  Barry S. Ticho, Dravet Syndrome, Epilepsy, STK-001, Stoke Therapeutics, US FDA, US Food and Drug Administration, USA