Calcitonin gene-related peptide (CGRP) is a signaling neuropeptide released from 
activated trigeminal sensory afferents in headache and facial pain disorders. 
There are a handful of CGRP-targeted therapies currently in phase 3 studies for 
migraine acute treatment or prevention. Currently, 4 monoclonal antibodies 
targeting either the CGRP ligand or receptor are being studied for migraine 
prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), 
and TEV-48125 (fremanezumab). Meanwhile, 1 small-molecule CGRP receptor 
antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute 
treatment of migraine. Two of these anti-CGRP monoclonal antibodies are in 
clinical trials for cluster headache prevention as well. Several other 
small-molecular CGRP receptor antagonists are in earlier stages of development 
for acute migraine treatment or prevention. In this review, we will discuss the 
growing body of clinical trials studying CGRP-targeted therapies for migraine 
and cluster headache.