First Patient Enrolled in Phase 2 Trial of EPX-100, Potential Add-on Therapy for Dravet
The first patient has been enrolled in Epygenix Therapeutics’ multicenter Phase 2 clinical trial that will assess the effectiveness and safety of EPX-100 as an add-on therapy in children with Dravet syndrome whose seizures are not fully controlled by other anti-epileptic medications.
The company is recruiting 24 children and adolescents, ages 2–17, with Dravet to participate in the 20-week proof-of-concept study (NCT04462770). Information on eligibility and recruiting sites is available here, as well as through the Dravet Syndrome Foundation’s website.
“We are very excited about the first patient enrollment because this is one of the most significant clinical milestones for us. This opens the door to explore the efficacy for a better treatment option, and confirms our commitment to [the] Dravet community,” Hahn-Jun Lee, PhD, president and CEO of Epygenix, said in a press release.
Originally used as an antihistamine to treat itchiness, EPX-100 (originally known as clemizole) now is being investigated as a potential therapy for Dravet after a study in a zebrafish model of the disease found the therapy was a potent seizure suppressor.
“First patient enrollment is an extremely exciting culmination and validation of our zebrafish-based drug discovery platform,” said Scott Baraban, PhD, professor at the University of California San Fransico, and first author of the zebrafish study.
“Our early promise to find new drugs for children suffering with Dravet Syndrome in a rapid and efficient manner is now coming to fruition. Working with Epygenix to move these preclinical discoveries to the clinic, in only a few short years, is a prime example of our ‘aquarium-to-bedside’ philosophy,” he added.
While the mechanism of action that enables EPX-100 to suppress seizures is still unclear, it is thought to be different from what gives the medication its antihistaminic properties, possibly involving serotonin signaling pathways. Serotonin is a brain chemical that participates in several signaling cascades, which are thought to be altered in people with Dravet.
This trial was supported by results from a Phase 1 trial (NCT04069689) that showed EPX-10 was safe and well-tolerated in healthy individuals when given in increasing single and multiple oral doses.
To be eligible to participate in the new Phase 2 trial, participants must have experienced their first seizure before reaching 18 months old, and carry a mutation in the SCN1A gene, the underlying cause of Dravet in most cases.
The 20-week study will begin with a four-week observational phase to assess eligibility and measure seizure frequency. Participants then will be assigned randomly to receive either an oral solution of EPX-100 or a placebo.
This will be followed by a four-week phase that will attempt to determine the maximum tolerated dose of the medication in each patient, starting at a daily dose of 2.0 mg/kg, with 1 mg/kg increments every seven days. After that, patients will enter a 12-week maintenance phase and, once completed, also will have the chance to join a 52-week open-label extension study.
The primary goal of the study will be to assess the percent change in the 28-day seizure frequency in the final four weeks of the 12-week maintenance phase, compared with the observational phase, in patients receiving EPX-100 and a placebo.
Secondary goals will include assessing the percentage of patients attaining 25% and 50% reductions in seizure frequency, determining the number of days participants experienced no seizures, and evaluating the effects of treatment on quality of life.
“We are all very excited that we can finally test our drug for its efficacy with patients. Through this clinical trial, the company hopes to quickly provide the best drug that is both safe and efficacious for [the Dravet syndrome] community,” said Alex Yang, chair of Epygenix’s board.
The company also announced its intentions to expand the development of EPX-100 to include other forms of epilepsy, such as Lennox-Gastaut syndrome.
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