EPX-100 Shows Promising Seizure Reduction in Ongoing Open-Label Extension

New data from the open-label extension (OLE) of the ongoing Phase 3 ARGUS (NCT04462770) trial show that EPX-100 (clemizole), developed by Harmony Biosciences, produced a median 50% reduction in countable motor seizure frequency in a cohort of patients with Dravet Syndrome (DS). Researchers say the results reinforce EPX-100’s favorable benefit-risk profile and highlight its potential as a new treatment option for DS.¹

Data from the OLE, presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9, in Atlanta Georgia, showed that 50% (n = 9) of the 18 participants achieved at least a 50% reduction in countable motor seizure frequency per 28 days (CMS-28). In terms of safety, EPX-100 was generally well-tolerated, including patients who had received treatment for more than 2 years and are approaching 3 years in the OLE phase.

Among participants, the most common treatment emergent adverse events (TEAEs; > 5%) were seizures, pyrexia and upper respiratory tract infection. Additionally, there were no significant gastrointestinal adverse events (2%), and no additional laboratory testing or special monitoring is required for the trial.

“The ARGUS trial is one of the most advanced development programs in the 5-HT2 (serotonin) agonist class and the effectiveness, safety and tolerability data of EPX-100 dosed BID from the open-label extension study are very encouraging,” said Kumar Budur, MD, MS, Chief Medical and Scientific Officer at Harmony Biosciences, in a statement. “These initial results support the advancement of our epilepsy franchise as we progress toward the topline data readout from the ARGUS trial in 2026.”¹

EPX-100 is an investigational therapy being studied for the treatment of Dravet syndrome (DS) in the ARGUS trial and Lennox-Gastaut syndrome (LGS) in the LIGHTHOUSE trial. The drug, discovered using a proprietary zebrafish drug screening platform, works by targeting central 5-hydroxytryptamine 2 (5HT-2) serotonin receptors to modulate serotonin signaling and is administered orally twice daily in a liquid formulation.

In its preclinical model, genetically modified scn1Lab zebrafish replicated the genetic mutations and seizure characteristics seen in most patients with DS. These zebrafish expressed voltage-gated sodium channels (Nav1.1) in the central nervous system, allowing researchers to quickly screen compounds for their potential to reduce seizures.

READ MORE: AES Poster Showcases Feasibility of Mobile App to Track Daily Self-Reporting Epilepsy Outcomes

Safety results from the trial showed 139 recorded treatment-emergent adverse events (TEAEs) in 21 patients (87.5%), of which 28 (33.3%) were deemed related to EPX-100. Upper respiratory tract infection, found in 13.7% of treated patients, was the most common TEAE, followed by generalized tonic-clonic seizure (7.9%), pyrexia (7.2%), and change in seizure presentation (6.5%).²

Prior to ARGUS, EPX-100 was assessed in a phase 1 study of adult healthy volunteers aged 24 to 50 years. The early-stage trial enrolled 24 healthy volunteers, testing multiple oral doses (20, 40 and 80 mg BID) of EPX-100 vs placebo over a 12-day period.

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REFERENCES
1. Harmony Biosciences Presents Clinically Meaningful Open-Label Extension Study Effectiveness Data for EPX-100 in Dravet Syndrome. Harmony Biosciences. News release. December 8, 2025. Accessed December 9, 2025. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-presents-clinically-meaningful-open-label
2. Ray A, Nomikos G, Rapchak KD, et al. ARGUS: a phase 3 study of EPX-100 (clemizole hydrochloride) as adjunctive therapy in patients with Dravet syndrome. Presented at: International Epilepsy Congress; August 30-September 3, 2025; Lisbon, Portugal.
3. Rao L, Masuoka L, Lee H, Baraban S. EPX-100 as an adjunctive therapy in Dravet syndrome: phase 1 and phase 2 randomized, double-blind, placebo-controlled trials. Presented at: 2022 AES Annual Meeting. Abstract 2.244.