Revolutionary Breakthrough in Epilepsy Treatment

A new Phase 3 clinical trial (NCT05066217) is set to evaluate the effectiveness and safety of EPX-100, a first-generation antihistamine developed by Harmony Biosciences, as a potential treatment for Lennox-Gastaut syndrome (LGS)—an extremely rare and severe form of epilepsy.

Trial Overview and Goals

The study aims to enroll patients aged 2 years and older diagnosed with LGS. Participants will undergo a rigorous 20-week monitoring period, with the possibility of continuing into an open-label extension after the maintenance phase.

Scheduled to be presented at the prestigious 2025 American Academy of Neurology (AAN) Annual Meeting in San Diego from April 5-9, this trial features a multi-phase design: a 4-week observation phase, a 4-week titration phase to find the optimal dosage, and a subsequent 12-week maintenance phase.

Examining Seizure Reduction

The primary endpoint for the study is the percentage change in the Clinical Mini-Mental Scale (CMMS-28) from baseline through the conclusion of the double-blind phase. Additionally, researchers will evaluate key safety parameters, including the frequency and severity of adverse events (AEs).

What’s at Stake

Dr. Kumar Budur, the study's senior author and chief medical officer at Harmony, stated that the trial will also explore numerous secondary endpoints, including the proportion of participants achieving at least a 50% reduction in seizure frequency and improvements measured by the Clinician Global Impression of Change (CGI-C) scale.

To qualify for the study, patients must have experienced onset of seizures prior to age 11, exhibit significant seizures leading to falls, and have shown inadequate responses to existing antiseizure therapies.

Strict Enrollment Criteria

Potential candidates for the trial are subject to strict eligibility criteria, including a stable regimen of any ongoing epilepsy treatments for at least 30 days prior to screening. Patients with a history of hypersensitivity to EPX-100 or those who have recently participated in other investigational trials will be excluded.

A Look into EPX-100's History

EPX-100, known scientifically as clemizole hydrochloride, has a rich history dating back to the 1950s when it was first approved as an antihistamine for allergies like hay fever. Over the years, researchers have uncovered its potential to modulate serotonin pathways, revealing its ability to combat hyperexcitability in the nervous system. This led to clemizole being considered as a therapeutic agent for seizure disorders, given its positive effects on calcium signaling.

A Promising Future

After Harmony Biosciences acquired Epygenix in mid-2024, they redoubled efforts on EPX-100, which is also being studied for its effects on Dravet syndrome in another Phase 3 study (NCT04462770). Previous Phase 1 trials indicated that EPX-100 was well-tolerated among healthy adults, with mild side effects such as drowsiness at higher doses.

Stay Updated

As we await the results from this groundbreaking trial, EPX-100 could potentially change the landscape of treatment options for patients suffering from Lennox-Gastaut syndrome and other related seizure disorders. More updates will be shared as this exciting research unfolds at the upcoming AAN 2025 meeting.