Stoke Therapeutics’ STK-001 Granted Orphan Drug Designation by FDA
The company now intends to test STK-001 in a Phase 1/2 clinical study in the first half of 2020.
“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,” Barry S. Ticho, MD, chief medical officer of Stoke Therapeutics, said in a press release.
“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,” he added.
Most patients (approximately 85%) with Dravet syndrome have mutations in one of the two copies of the SCN1A gene, which provides instructions for making sodium channels. The gene encodes for one part, called the alpha subunit, of a specific sodium channel known as NaV1.1. Located on the surface of nerve cells, this sodium channel is required to generate and transmit electrical signals within the brain.
Available therapies do not address the underlying genetic cause of Dravet syndrome.
STK-001 is an antisense oligonucleotide, or ASO, which can promote the production of proteins that are faulty, or whose levels are insufficient.
ASOs are specifically designed to bind to a desired RNA sequence. There, they support the conversion of a nonproductive RNA molecule into a functional one. This strategy takes advantage of a naturally occurring process, called RNA splicing. Immature RNA sequences are processed by the removal of small bits of sequence to generate a functional protein-coding sequence.
Specifically, STK-001 works by increasing the levels of the NaV1.1 protein from the functional (non-mutated) SNCA1 gene. This restores the NaV1.1 protein to near-normal levels, thereby reducing seizures and other disease symptoms.
Pre-clinical studies have shown that this antisense oligonucleotide can increase the levels of SCNA1 in human neurons grown in the lab. Furthermore, in mouse models of Dravet syndrome, the compound restored NaV1.1 protein levels in the brain and decreased the number of seizures and sudden unexplained death in epilepsy (SUDEP) cases.
“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,” Ticho said.
Orphan drug designation is given to encourage the development of therapies for rare diseases, characterized as those that affect less than 200,000 people in the U.S. The FDA status provides multiple benefits, including seven years of market exclusivity for the therapy, exemption from FDA application fees, and tax credits for clinical trials.