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CGRP-Targeting Peptide Therapies Are Transforming Migraine Prevention

evidence
The takeaway

Six CGRP-targeting therapies — four monoclonal antibodies and two gepants — are now available for preventive migraine treatment, offering strong efficacy with favorable safety profiles.

6 approved drugs

CGRP-targeted medications now available for preventive migraine treatment — four injectable antibodies and two oral gepants, all introduced since 2018

What the researchers found

Six drugs targeting CGRP are now approved for preventive treatment of episodic migraine in adults: four monoclonal antibodies (eptinezumab, erenumab, fremanezumab, galcanezumab) and two gepants (rimegepant, atogepant). The monoclonal antibodies and atogepant have demonstrated effectiveness for both episodic and chronic migraine. All CGRP-targeted therapies show favorable safety and tolerability profiles.

These therapies have enabled new paradigms for migraine prevention, moving beyond older drugs that were repurposed from other conditions toward purpose-built treatments designed specifically around the CGRP peptide pathway.

Why it matters

Migraine affects over 1 billion people globally and was historically treated with preventive medications borrowed from other conditions (blood pressure drugs, antidepressants, anti-seizure medications) that often had significant side effects. CGRP-targeted therapies represent the first class of medications designed specifically for migraine, targeting the peptide pathway now known to play a central role in migraine pathophysiology.

How the study worked

This is a clinical review article published in Continuum, a continuing medical education journal of the American Academy of Neurology. It synthesizes clinical trial evidence and clinical experience with CGRP-targeted therapies for migraine prevention, providing a comprehensive overview for practicing neurologists.

What this study cannot tell us

As a review article, this does not present new primary data. The article focuses primarily on CGRP-targeted therapies and may not provide equal coverage of all available preventive migraine treatments. Long-term safety data beyond a few years is still accumulating for these relatively new medications. Cost and access remain barriers for many patients.

How to read the evidence

This is a clinical review synthesizing evidence from multiple randomized controlled trials. While it does not generate new data, the individual CGRP-targeted therapies it reviews have strong RCT evidence supporting their efficacy. The review provides a high-quality clinical synthesis for practicing physicians.

When this study was published

Published in 2024, this review covers the current state of CGRP-targeted migraine prevention including all agents available as of publication. The field continues to evolve rapidly.

The bigger picture

The success of CGRP-targeted therapies is one of the most significant examples of peptide biology translating into transformative clinical medicine. The rapid development and adoption of multiple CGRP-targeting drugs since 2018 validates the concept that targeting specific neuropeptide pathways can yield effective, well-tolerated treatments for neurological conditions — a model that could be applied to other neuropeptide-driven disorders.

Questions still open

  • How do the different CGRP-targeting approaches (antibodies vs. gepants) compare in long-term effectiveness and patient preference?
  • Will combination approaches using CGRP therapies with other preventive treatments provide additional benefit for treatment-resistant migraine?
  • Can CGRP-targeted therapies be personalized based on individual patient biomarkers or migraine subtypes?

Common questions

What is CGRP and why is it important in migraine?
CGRP (calcitonin gene-related peptide) is a neuropeptide released by nerve cells during migraine attacks. It causes blood vessel dilation and inflammation in the brain's covering, contributing to migraine pain. Blocking CGRP or its receptor with antibodies or gepant medications can prevent or reduce migraine attacks.
What is the difference between monoclonal antibodies and gepants for migraine?
Monoclonal antibodies (like erenumab and fremanezumab) are injectable proteins given monthly or quarterly that block CGRP or its receptor for extended periods. Gepants (like rimegepant and atogepant) are oral small-molecule drugs that block the CGRP receptor and can be used for both prevention and acute treatment of migraine.

Read the original research

Preventive Treatment of Migraine.

Continuum (Minneapolis, Minn.), 30(2), 364-378

Citation

Lipton, Richard B. (2024). Preventive Treatment of Migraine.. Continuum (Minneapolis, Minn.), 30(2), 364-378. https://doi.org/10.1212/CON.0000000000001418