EPX-100 is a potential new treatment being developed by Epygenix Therapeutics for people with Dravet syndrome.

How does EPX-100 work?

Dravet syndrome is a rare and severe form of epilepsy characterized by prolonged seizures, often happening numerous times each day. It is known that the disease is caused by a mutation in the SCN1A gene, but it is not fully understood how this mutation leads to the development of seizures.

EPX-100 is a repurposed antihistamine, which was used in the 1950s and 1960s to treat itchiness. The medication is thought to be able to suppress seizures through its action on the serotonin signaling pathways, a mechanism that is different from its anti-histaminic properties.

Serotonin is a chemical messenger present in many parts of the brain. Scientists think that people with Dravet syndrome may have alterations in the serotonin signaling pathway, but the exact problems are not known. Likewise, precisely how EPX-100 affects serotonin systems in the brain to reduce seizures is still unclear.

EPX-100 in clinical trials

EPX-100 was discovered in a study that tested more than 3,000 approved medications in zebrafish models of Dravet syndrome. Among these, EPX-100 was found to be a powerful suppressor of seizures. The results of this study were published in the journal Nature Communications in 2013.

A placebo-controlled, double-blind, two-part Phase 1 clinical trial (NCT04069689) tested the safety and pharmacokinetics — the movement in the body — of oral EPX-100 in 24 healthy volunteers. The participants were divided into three groups of eight. Six participants in each group received EPX-100 at three different doses (20, 40, or 80 mg), while two received placebo.

During the first part of the study, the participants were admitted to the hospital and given an initial oral dose of EPX-100 or placebo. Their blood samples were taken periodically throughout the day. Five days after that initial dose, the individuals were started on twice-daily doses of EPX-100 or placebo and had their blood taken once a day. Then, on Day 12, participants were given a single dose of EPX-100 or placebo again, with blood samples taken periodically over the next 24 hours before they were discharged. At the end of the study’s first part, the participants were sent home for a week before being readmitted to the hospital.

In the study’s second part, the participants were given a high-fat meal and then administered EPX-100 or placebo after 30 minutes to see how food affects pharmacokinetics. Blood samples were again taken periodically for the next 24 hours before the participants were discharged.

Epygenix announced in January 2020 that it had completed the study and that the results showed that EPX-100 was safe and well-tolerated by both male and female participants. Pharmacokinetics also were consistent with animal studies and proportional to the dose received.

The company is now preparing Phase 2 efficacy studies to test EPX-100 in patients with Dravet syndrome in the U.S. and Australia.

Other information

The U.S. Food and Drug Administration (FDA) designated EPX-100 an orphan drug in April 2017. This program is designed to promote the development of new therapies for rare diseases. Two years later, in July 2019, the FDA granted the treatment investigational new drug status to treat Dravet syndrome. That designation allowed Epygenix to start human clinical trials.

The company also announced its intentions to expand EPX-100’s development to include other forms of genetic epilepsy, such as infantile spasms, Lennox-Gastaut syndrome, and Ohtahara syndrome.


Last updated: Jan. 29, 2020


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