A systematic review with expert opinion on the role of gepants for the preventive and abortive treatment of migraine

ABSTRACT

Introduction

Gepants are small molecules targeting the calcitonin gene-related peptide (CGRP) that have been recently introduced and are under additional clinical development as preventive and abortive treatment options for migraine.

Areas covered

After providing a narrative overview of current preventive and acute treatment options for migraine and summarizing the pathophysiology of migraine attack and the role of CGRP, we performed a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, on trials on gepants in preventive and acute treatment of migraine. Studies and results were reviewed and discussed, and expert opinion was presented. We also collected data on relevant ongoing trials.

Expert opinion

Whether direct targeting CGRP pathways within the central nervous system or indirectly modulating them from the peripheral nervous system is more effective and safer in migraine remains still unclear. The available data on the efficacy and safety of gepants suggest they may represent an abortive, and to some extent, preventive treatment option for migraine, in patients who do not respond or have adverse effects to first/second line treatments or at high risk for medication overuse headache; thus opening new therapeutic horizons.

KEYWORDS:

• Migraine
• treatment
• calcitonin gene-related peptide receptor
• rimegepant
• telcagepant
• ubrogepant
• atogepant
• zavegepant
• olcegepant

Article highlights

• Gepants are small calcitonin gene-related peptide (CGRP) receptor antagonist molecules that hold promise as acute migraine treatment when triptans are contraindicated

• Second-generation gepants (ubrogepant, rimegepant) have demonstrated considerable efficacy and safety as abortive anti-migraine therapies

• Novel fast-acting third-generation gepants (zavegepant, FE205030) are under study as abortive anti-migraine therapies

• Telcagepant, rimegepant, and atogepant may be effective for migraine prevention

• Ongoing studies comparing head-to-head gepants and established preventive and acute migraine treatments will offer precious information

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have previously served as a consultant for Supernus Pharmaceuticals, Inc. and Trillen Medical Inc., and have received research grants from the NIH. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.