Calcitonin Gene-Related Peptide (CGRP) is now firmly established in migraine pathophysiology. A number of lines of evidence support this:
- CGRP levels (both peripherally and centrally) increase during a severe migraine attack
- Elevated CGRP levels during a migraine attack are normalised with effective triptan treatment
- Intravenous infusion of CGRP can induce migraine-like attacks in patients with a history of migraine
- Administration of CGRP receptor antagonists has been shown to abort an attack
These findings have driven the development of new agents specifically targeting CGRP or its receptor, eg. erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), eptinezumab (Vyepti), for migraine prevention. Small molecule CGRP receptor antagonists or ‘gepants’ have also been approved, eg. rimegepant (Nurtec ODT/Vydura) and ubrogepant (Ubrelvy) for acute treatment of migraine, and atogepant (Qulipta) and rimegepant (Nurtec ODT/Vydura) for migraine prevention.
Some currently available agents are being investigated in other indications, and other novel agents that target CGRP are in development.