Epygenix Therapeutics is planning to launch a Phase 2 clinical trial testing EPX-100 in patients with Dravet syndrome, after Phase 1 results showed the investigational therapy was safe and well tolerated in healthy volunteers.
EPX-100 is a repurposed antihistamine, originally known as clemizole, which was used in the 1950s and 1960s to treat itchiness. The compound was found to be a strong suppressor of spontaneous convulsive behavior in fish models of Dravet syndrome. It is thought to suppress seizures through its action on the serotonin signaling pathways, which work differently than its antihistaminic properties.
Serotonin is a chemical messenger present in many parts of the brain. While it is thought that people with Dravet may have alterations in their serotonin signaling pathways, the precise manner in which EPX-100 affects serotonin systems in the brain to reduce seizures is still unclear.
The randomized Phase 1 trial (NCT04069689) explored the safety and tolerability of escalating doses of EPX-100 and consisted of two parts. The first evaluated EPX-100’s safety and pharmacokinetics, which is essentially how the body affects a medicine. The second assessed how food affects the stability and bioavailability of EPX-100 in the body and on different treatment regimens.
In the first part of the trial, different concentrations of EPX-100 were given to 24 participants — 12 men and 12 women. Three groups of six people were given either 20, 40, or 80 mg of EPX-100, and six people were given a placebo while on a fasting state.
Blood samples were taken at regular intervals to measure the pharmacokinetics. Seven days later, the participants were given EPX-100 or a placebo twice a day for three days, and again blood samples were monitored. On day 12 of the study, the participants were given a single dose of EPX-100 or placebo, and were monitored for another 24 hours.
The second part of the study took place one week later, after a washout period. Thirty minutes after eating a high-fat meal, the participants were given a single dose of EPX-100 (either 20, 40, or 80 mg) or a placebo, and blood samples were taken over 24 hours.
Results confirmed that EPX-100 was safe, well-tolerated, and did not show any clinically significant abnormalities among participants.
Based on these positive results, Phase 2 testing in Dravet patients will now begin in collaboration with Greenlight Clinical, a contract research organization specializing in clinical trials.
“We are very excited about the successful completion of EPX-100 Phase 1 studies because we were able to confirm the safety and tolerance of EPX-100 in humans and obtain invaluable PK [pharmacokinetics] information for upcoming Phase 2 studies. Indeed, this will be a big momentum for EPX-100 development for the treatment of Dravet patients,” Hahn-Jun Lee, PhD, Epygenix’s president and CEO, said in a press release.
The pharmacokinetics data was dose-proportional, meaning it changed as EPX-100’s dosage increased, and matched that of preclinical animal studies.
“The results of these Phase 1 trials confirm a safe EPX-100 profile already predicted from preclinical studies. We are excited to now see this compound, first discovered in a zebrafish model of Dravet, move into human efficacy trials,” said Scott C. Baraban, PhD, professor at University of California, San Francisco, and chair of the scientific advisory board at Epygenix.
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