Taking a patient-first, precision medicine approach to orphan drug development
Epygenix Therapeutics is a precision medicine biotech company developing drugs to treat Dravet syndrome and other rare forms of genetic epilepsy. Recognizing the unmet needs of patients with these diseases, Epygenix has adopted a drug-repurposing strategy intended to accelerate research and development, and is approaching the start of a phase 1/2 trial of its lead candidate.
The lead candidate, EPX-100, is a first-generation antihistamine with a long history of safe use. Epygenix identified the potential to use the drug to treat Dravet syndrome by screening 3,000 approved drugs in genetically modified zebrafish, a species that shares many targets and pathways with humans and provides a faster, cheaper route to clinical trials than rodents. Such time savings are vital given the poor health outcomes and major unmet need of people with Dravet syndrome.
Scott C. Baraban, a professor at the University of California, San Francisco, and one of Epygenix’s scientific advisors, directed the zebrafish-screening laboratory. Baraban’s screening singled out three candidates as potential treatments for Dravet syndrome, an ultra-orphan disease that causes severe convulsions and typically results in death by the age of six. In the case of EPX-100, tests in zebrafish and subsequent radioligand-binding assays showed that the antihistamine suppressed spontaneous convulsions and electrographic seizures by modulating serotonin signaling pathways.
Epygenix has secured an orphan drug designation (ODD) and is preparing an investigational new drug (IND) application to submit to the US Food and Drug Administration (FDA) for EPX-100. Epygenix expects to file an IND for a phase 1/2 trial of EPX-100 in the first quarter of 2018, setting it on a path that hopefully will lead to approval through the 505(b)(2) pathway.
Epygenix’s near-term focus is on EPX-100, but its mission to provide Dravet patients with multiple treatment options has led it to research other molecules. One of these, EPX-200, has also received ODD and has advanced as far as compassionate use in humans.
Physicians tested EPX-200 in five people with medically intractable Dravet syndrome. All five patients experienced fewer seizures while taking the approved serotonin-receptor agonist. This validated the zebrafish-to-human screening strategy and suggested that EPX-200 warrants further investigation in Dravet syndrome. The planned phase 1/2 trial of EPX-100 could further validate Epygenix’s pipeline.
As Epygenix advances EPX-100, it also is considering opportunities to expand into other forms of genetic epilepsy, including Lennox–Gastaut syndrome, infantile spasm, and Ohtahara syndrome.
Epygenix’s plans to broaden the scope of its development program are in keeping with its goal of bringing effective treatment options to many patients with rare forms of genetic epilepsy as quickly as possible
Hahn-Jun Lee, President and CEO
Epygenix Therapeutics, Inc.
Paramus, New Jersey, USA