This review chronicles how targeting the peptide CGRP led to a new class of migraine drugs, culminating in erenumab becoming the first FDA-approved monoclonal antibody for migraine prevention in 2018.
First-in-class approval: May 2018Erenumab (Aimovig) became the first monoclonal antibody approved by the FDA for migraine prevention, opening a new therapeutic era
What the researchers found
This comprehensive review traces the development of anti-CGRP therapies from the first proof-of-concept with olcegepant in 2004 to the FDA approval of erenumab in May 2018 — the first monoclonal antibody approved for migraine prevention. It summarizes randomized controlled trial data for four anti-CGRP monoclonal antibodies (erenumab, galcanezumab, fremanezumab, eptinezumab) and two small-molecule gepants (ubrogepant, rimegepant) for acute migraine treatment.
Galcanezumab also showed effectiveness in preventing episodic cluster headache, expanding the potential uses of this drug class beyond migraine.
Why it matters
For decades, migraine patients relied on medications that were developed for other conditions (blood pressure drugs, antidepressants, anti-seizure drugs). Anti-CGRP therapies were the first treatments designed specifically for migraine based on understanding the biology of the disease. This review captures the moment that era began.
The numbers in context
Erenumab FDA approved: May 17, 2018 · 4 monoclonal antibodies in development · 2 gepants completed pivotal trials · First gepant proof-of-concept: 2004
How the study worked
Narrative review of the translational research pathway, pathophysiology, and all accessible randomized controlled trials, abstracts, platform presentations, and press releases on anti-CGRP monoclonal antibodies and gepants through May 2018.
Who was studied
Review covering clinical trial populations with episodic and chronic migraine, and episodic cluster headache
What this study cannot tell us
Written in May 2018, this review captures only the earliest clinical data. Several of the drugs discussed were still awaiting FDA decisions at the time of publication. Long-term safety and real-world effectiveness data were not yet available. As a single-author narrative review, it does not use systematic review methodology.
How to read the evidence
Rated strong because this review synthesizes data from multiple randomized controlled trials across several anti-CGRP drugs, covering both the mechanistic rationale and clinical evidence that led to FDA approval.
When this study was published
Published in 2018, this review captures the pivotal moment when anti-CGRP drugs were first reaching the market. Since then, all drugs discussed have been approved and extensive real-world data has accumulated, but this remains a valuable historical and scientific reference.
The bigger picture
Anti-CGRP therapies represent one of the clearest success stories in translational peptide research — taking a basic science discovery about a neuropeptide's role in pain and turning it into an entirely new drug class. Since this review was published, all four antibodies and both gepants have been approved, and newer CGRP-targeting drugs continue to emerge. This class has fundamentally changed how migraine is treated.
Questions still open
- What are the long-term effects of chronically blocking CGRP, given that the peptide plays roles beyond pain signaling?
- Will anti-CGRP therapies prove effective for other headache disorders beyond migraine and cluster headache?
- How do the injectable antibodies compare to the oral gepants in terms of patient preference and adherence?
Common questions
What is CGRP and why does blocking it help migraines?
What's the difference between anti-CGRP antibodies and gepants?
Read the original research
History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment.
Headache, 58 Suppl 3, 238-275
Citation
Tepper, Stewart J. (2018). History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment.. Headache, 58 Suppl 3, 238-275. https://doi.org/10.1111/head.13379