Four monoclonal antibodies targeting the peptide CGRP or its receptor — erenumab, galcanezumab, fremanezumab, and eptinezumab — represent the first drugs specifically designed to prevent migraine attacks.
4 antibodiesErenumab, galcanezumab, fremanezumab, and eptinezumab — the first drugs targeting CGRP specifically for migraine prevention
What the researchers found
Four monoclonal antibodies targeting the CGRP pathway have been approved for migraine prevention:
- Erenumab: targets the CGRP receptor
- Galcanezumab: targets the CGRP peptide
- Fremanezumab: targets the CGRP peptide
- Eptinezumab: targets the CGRP peptide
These are the first drugs specifically developed for migraine prevention, replacing reliance on repurposed medications from other therapeutic areas.
Why it matters
Before anti-CGRP antibodies, migraine prevention was limited to drugs borrowed from other fields — beta-blockers, antidepressants, and antiepileptics — which often had significant side effects and modest efficacy. The development of drugs that specifically target the CGRP peptide pathway represents the first mechanism-based approach to migraine prevention, offering improved tolerability and a treatment rationale grounded in migraine biology.
How the study worked
This is a clinical review article published in the Cleveland Clinic Journal of Medicine summarizing the pharmacology, mechanism, and clinical role of anti-CGRP monoclonal antibodies for migraine prevention.
What this study cannot tell us
The abstract provides only a brief overview without specific efficacy data, response rates, or side effect profiles. As a review published in 2020, it does not cover subsequent developments like gepants, newer delivery methods, or long-term real-world effectiveness data. The cost and access barriers to monoclonal antibody therapies are not discussed.
How to read the evidence
This is a clinical review article providing an overview of CGRP-targeting antibodies. The underlying evidence includes phase 3 randomized controlled trials, but this paper itself is a narrative summary without original data.
When this study was published
Published in 2020, this review captures the early era of anti-CGRP antibodies. The field has since expanded with additional drugs and extensive real-world data confirming these therapies' effectiveness.
The bigger picture
The anti-CGRP antibodies launched a new era in migraine medicine. Since 2020, the field has expanded further with small-molecule CGRP receptor antagonists (gepants like rimegepant and atogepant) and CGRP-targeted drug delivery innovations. The identification of CGRP as the central peptide in migraine pathophysiology ranks among the most important discoveries in headache medicine and has been validated by the clinical success of these targeted therapies.
Questions still open
- How do the four anti-CGRP antibodies compare to each other in terms of efficacy and side effects?
- Are oral CGRP receptor antagonists (gepants) equally effective as the injectable antibodies for migraine prevention?
- What happens to patients who don't respond to anti-CGRP therapy — is there a different mechanism driving their migraines?
Common questions
What is CGRP and why does blocking it prevent migraines?
Why were these drugs called 'long overdue'?
Read the original research
CGRP antagonists for decreasing migraine frequency: New options, long overdue.
Cleveland Clinic journal of medicine, 87(4), 211-218
Citation
Bucklan, Julia; Ahmed, Zubair. (2020). CGRP antagonists for decreasing migraine frequency: New options, long overdue.. Cleveland Clinic journal of medicine, 87(4), 211-218. https://doi.org/10.3949/ccjm.87a.19048