Rimegepant: A Comprehensive Pharmacological and Clinical Review of an Oral CGRP Receptor Antagonist for Migraine Treatment and Prevention

Abstract

Rimegepant, an orally administered small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, represents a significant advancement in migraine pharmacotherapy. Developed initially by Biohaven Pharmaceuticals and now part of Pfizer's portfolio, rimegepant has achieved the novel distinction of being the first oral agent approved by both the U.S. Food and Drug Administration (FDA) and the European Commission (EC) for the dual indications of acute treatment of migraine with or without aura and the preventive treatment of episodic migraine in adults. Its mechanism of action involves selectively blocking CGRP receptors, thereby inhibiting the effects of CGRP, a key neuropeptide implicated in migraine pathophysiology. Pharmacokinetically, rimegepant exhibits good oral bioavailability, an 11-hour half-life suitable for its dual dosing regimens, and metabolism primarily via CYP3A4. Pivotal Phase 3 clinical trials have demonstrated its efficacy in providing pain freedom and relief from most bothersome symptoms in acute migraine attacks, as well as reducing monthly migraine days in episodic migraine prevention. Notably, rimegepant possesses a favorable safety and tolerability profile, characterized by a lack of vasoconstrictive effects—a crucial advantage over triptans, particularly for patients with cardiovascular contraindications—and no evidence of hepatotoxicity. This comprehensive review details the chemical properties, regulatory journey, pharmacological profile, clinical efficacy, safety, and therapeutic positioning of rimegepant in the evolving landscape of migraine management.

1. Introduction: The Evolving Landscape of Migraine Therapy and the Advent of Rimegepant

1.1. Migraine: A Disabling Neurological Disorder and Unmet Therapeutic Needs