To evaluate safety and efficacy of EPX-100 as adjunctive therapy in participants with Dravet Syndrome.

ARGUS, a phase 3, randomized, double-blind (DB), placebo-controlled trial was initiated to assess EPX-100 as adjunctive therapy in participants with DS. Participants who complete the DB phase can enroll in an open-label extension (OLE) phase investigating the long-term safety and tolerability of EPX-100.

EPX-100 is a 5HT2 (serotonin) receptor agonist identified as having antiseizure activity using the Scn1a zebrafish model for Dravet Syndrome (DS).

OLE participants had met the ARGUS trial inclusion criteria: age ≥2 years and older, clinical diagnosis of DS, onset of seizures prior to 18 months of age, not controlled on current stable regimen of antiseizure medications (ASM), Scn1a pathogenic variant, ≥4 countable motor seizures per 28-day (CMS-28) baseline.   

Eligible participants were randomly assigned (1:1) to receive EPX-100 oral solution (weight-based dosing: 1-4 mg/kg BID, max 80 mg BID) or placebo, in a blinded manner over a 16-week period. Participants who complete the DB phase are eligible to enter an optional 3-year OLE extension phase after a double dummy titration. 

As of July 2025, 34 participants who completed the DB phase elected to enroll in the ongoing OLE phase. Twenty participants have remained in the OLE for at least 6 months.

The most common TEAEs included seizure (14.5%), pyrexia (12%), and upper respiratory tract infection (11%). Preliminary effectiveness data demonstrates that participants who had at least 6-month OLE exposure to EPX-100 experienced, from DB Baseline to the first 6 months of the OLE, a CMS-28 mean reduction of −40.8% (SD: 44.9%) and median reduction of −49.2%.