Clemizole hydrochloride
An investigational treatment for Dravet Syndrome.
The same compound appears under different names depending on the context. Here is how to identify Clemizole hydrochloride wherever you encounter it, plus the key facts at a glance.
- Generic name
- Clemizole hydrochloride
- Development code
- EPX-100
- Drug class
- Serotonin receptor agonist (repurposed antihistamine)
- Manufacturer
- Harmony Biosciences
- How it's taken
- Taken by mouth as a liquid formulation, twice daily.
A repurposed 1950s antihistamine discovered through zebrafish drug screening to have potent anti-seizure properties. Now in Phase 3 trials for Dravet syndrome, clemizole works through serotonin pathways rather than its original antihistamine mechanism.
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How Clemizole hydrochloride works
Clemizole was originally an antihistamine from the 1950s, but researchers discovered using zebrafish (which share many genes with humans) that it powerfully suppresses seizures through serotonin pathways, not its antihistamine action. It activates serotonin 5-HT2 receptors in the brain, strengthening the circuits that prevent seizures.
Mechanism: 5-HT2 serotonin receptor agonist (originally a first-generation antihistamine) with anti-seizure activity mediated through serotonergic rather than antihistaminic pathways
Side effects and safety
In the ARGUS open-label extension, clemizole was generally well tolerated. Full side effect data will come from the placebo-controlled Phase 3 ARGUS results.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Clemizole hydrochloride
Taken by mouth as a liquid formulation, twice daily. The oral liquid form makes it easier to dose in children and patients who have difficulty swallowing pills.
Clinical trial results
The Phase 3 ARGUS trial (NCT04462770) is a placebo-controlled study in about 150 people aged 2 and older with Dravet syndrome. In its open-label extension, 18 participants with at least 6 months of treatment had a median 50% reduction in countable motor seizures (presented in December 2025). Harmony expects topline Phase 3 results in the first half of 2027. A second Phase 3 trial, LIGHTHOUSE, is testing it in Lennox-Gastaut syndrome.
Main registered trial: NCT04462770 on ClinicalTrials.gov. Check it for the current status, sites and contacts before asking about enrollment.
Development history
Clemizole was an antihistamine used in the 1950s. Epygenix Therapeutics, which Harmony Biosciences acquired in 2024, identified its anti-seizure properties using a zebrafish drug screen, leading to clinical development for Dravet syndrome under the code EPX-100.
Explore Dravet Syndrome trials
Other Dravet Syndrome treatments
Common questions about Clemizole hydrochloride
▸What is Clemizole hydrochloride?
A repurposed 1950s antihistamine discovered through zebrafish drug screening to have potent anti-seizure properties. Now in Phase 3 trials for Dravet syndrome, clemizole works through serotonin pathways rather than its original antihistamine mechanism.
▸How does Clemizole hydrochloride work?
Clemizole was originally an antihistamine from the 1950s, but researchers discovered using zebrafish (which share many genes with humans) that it powerfully suppresses seizures through serotonin pathways, not its antihistamine action. It activates serotonin 5-HT2 receptors in the brain, strengthening the circuits that prevent seizures.
▸What are the side effects of Clemizole hydrochloride?
In the ARGUS open-label extension, clemizole was generally well tolerated. Full side effect data will come from the placebo-controlled Phase 3 ARGUS results.
▸How is Clemizole hydrochloride taken?
Taken by mouth as a liquid formulation, twice daily. The oral liquid form makes it easier to dose in children and patients who have difficulty swallowing pills.
▸Is Clemizole hydrochloride FDA approved?
Clemizole hydrochloride is currently in phase 3 clinical trials for Dravet Syndrome. It has not yet received FDA approval.
▸How was clemizole discovered to work for seizures?
Researchers used zebrafish with SCN1A mutations (the same gene affected in Dravet syndrome) to screen 320 existing drugs for anti-seizure activity. Clemizole, a 1950s antihistamine, unexpectedly suppressed seizures in these zebrafish. Further work suggested the effect came through serotonin 5-HT2 receptors rather than the antihistamine pathway, which led to its development for Dravet syndrome.
▸What is the ARGUS trial?
ARGUS is the placebo-controlled Phase 3 trial of clemizole (EPX-100) in people aged 2 and older with Dravet syndrome. In its open-label extension, 18 participants with at least 6 months of treatment had a median 50% reduction in countable motor seizures. Harmony expects topline results in the first half of 2027.
▸Is clemizole the same as the old allergy medication?
It is the same molecule as the antihistamine used in the 1950s, but it is being developed for Dravet syndrome because of a different effect: its anti-seizure activity appears to come from serotonin receptors, not antihistamine action. For Dravet syndrome it is given as an oral liquid twice daily.
▸How does clemizole compare to other Dravet treatments?
Clemizole appears to act on serotonin 5-HT2 receptors, a pathway also involved in how fenfluramine works, though the 2 drugs are different. It has not yet shown efficacy in a placebo-controlled trial; the Phase 3 ARGUS results, expected in the first half of 2027, will show whether it works. If approved, it would add another option for Dravet patients.
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Harmony Biosciences · 2025-12-08. Harmony Biosciences Presents Open-Label Extension Study Effectiveness Data for EPX-100 in Dravet Syndrome. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-presents-clinically-meaningful-open-label
- ClinicalTrials.gov. ARGUS: EPX-100 (clemizole) in Dravet syndrome. https://clinicaltrials.gov/study/NCT04462770