Describe the rationale and design of a pivotal Phase 2 clinical trial of BHV-2100 for acute treatment of migraine.

Transient receptor potential melastatin 3 (TRPM3) is a calcium-permeable ion channel expressed in sensory neurons of the trigeminal ganglion and dorsal root ganglion involved in neuroinflammatory pain signal transmission. Preclinical evidence shows that TRPM3 antagonists and gene deletions reduce pain transmission, inhibit release of CGRP, and modulate activity of other known pain-associated TRP proteins. TRPM3 is co-expressed with migraine-relevant genes in the human trigeminal ganglion, and TRPM3 gene variants are associated with increased risk of migraine. BHV-2100 is an orally administered TRPM3 antagonist in development for pain and migraine that has demonstrated potent pain reversal in preclinical models and excellent safety, tolerability, and pharmacokinetic properties in Phase 1 clinical studies.

This is a pivotal Phase 2 randomized, double-blind, placebo-controlled study (NCT06603623) evaluating the efficacy and safety of BHV-2100 for acute treatment of migraine. Adults with 2-8 moderate/severe migraine attacks per month and <15 headache days per month are eligible. Participants are randomized 1:1:1 to a single oral dose of BHV-2100 75mg, 150mg, or placebo to treat a single migraine attack of moderate/severe pain intensity.

This study is ongoing and will enroll approximately 575 participants across 60 US sites. The coprimary endpoints are pain freedom and most bothersome symptom freedom at 2 hours postdose. Additional assessments include pain relief, normal function, and freedom from photophobia, phonophobia, and nausea at 2 hours; sustained pain freedom and sustained pain relief through 24 and 48 hours; drug plasma concentrations; and safety/tolerability.

TRPM3 is a novel target for the treatment of migraine and pain. BHV-2100 is a first-in-class TRPM3 antagonist being studied for acute treatment of migraine with the potential to address the needs of millions of patients who continue to seek better migraine relief.