History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment

Headache. 2018 Nov:58 Suppl 3:238-275. doi: 10.1111/head.13379. Epub 2018 Sep 22.


Objective - To briefly describe the history of and available data on anti-calcitonin gene-related peptide (CGRP) therapies for headache. Background - CGRP was proposed as a target for primary headache therapies. Translational research involved moving from delineating the relationships between CGRP and primary headaches and the clinical development of anti-CGRP treatments. The first anti-CGRP treatment, an intravenous CGRP-receptor antagonist or gepant, olcegepant, was described as effective in terminating migraines in humans in 2004. Methods - The author briefly reviews some of the pathophysiology and translational research that led to the development of the gepants initially and then subsequently to the anti-CGRP and anti-CGRP receptor monoclonal antibodies. All accessible randomized controlled trials, abstracts, platform presentations, and press releases on the monoclonal antibody trials are summarized. The trajectory from bench research to the approval of the first anti-CGRP receptor monoclonal antibody for clinical use in migraine prevention, erenumab, is discussed, as well as potential clinical uses of the anti-CGRP treatments. Results - The US Food and Drug Administration (FDA) approved erenumab, an anti-CGRP receptor monoclonal antibody, for prevention of migraine May 17, 2018. At the time of this writing (May 2018), 2 other anti-CGRP monoclonal antibodies have been submitted to the FDA for the indication of prevention of migraine, galcanezumab and fremanezumab. Galcanezumab has reportedly shown effectiveness in preventing episodic cluster headache as well, although has not yet been submitted to the FDA for this indication. Eptinezumab will likely be submitted to the FDA for prevention of migraine later in 2018. Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for acute treatment of migraine, but have not yet been submitted to the FDA for this indication. Conclusions - The development of anti-CGRP therapies opens a new era in the acute and preventive treatment of primary headache disorders.

Keywords: CGRP; calcitonin gene-related peptide; cluster headache; eptinezumab; erenumab; fremanezumab; galcanezumab; gepants; migraine; migraine preventive treatment; migraine prophylaxis; monoclonal antibodies; olcegepant; rimegepant; telcagepant; ubrogepant.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Calcitonin Gene-Related Peptide / antagonists & inhibitors*
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcitonin Gene-Related Peptide Receptor Antagonists / administration & dosage*
  • Clinical Trials as Topic / methods
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends
  • Humans
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / metabolism
  • Pyridines / administration & dosage
  • Pyrroles / administration & dosage
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • Translational Research, Biomedical / methods
  • Translational Research, Biomedical / trends*
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Pyridines
  • Pyrroles
  • Receptors, Calcitonin Gene-Related Peptide
  • ubrogepant
  • erenumab
  • Calcitonin Gene-Related Peptide