Calcitonin gene-related peptide (CGRP) is a signaling neuropeptide released from activated trigeminal sensory afferents in a headache and facial pain disorders. There are a handful of CGRP-targeted treatments currently in phase III studies for an acute migraine treatment or prevention.

At present, there are four monoclonal antibodies [ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab)] being studied for migraine prevention that target either the CGRP ligand or receptor.

In the meantime, one small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase III studies for the treatment of migraine. Among these, two of the anti-CGRP monoclonal antibodies are also in clinical trials for cluster headache prevention. Many other small-molecular CGRP receptor antagonists are in earlier developmental stages for the treatment or prevention of an acute migraine. The current review emphasizes on the growing body of clinical trials studying CGRP-targeted therapies for migraine and cluster headaches.