All four anti-CGRP monoclonal antibodies proved effective and safe for migraine prevention in early clinical trials, with up to 32% of patients becoming completely migraine-free.
Up to 32% complete migraine freedomIn phase II trials, up to a third of patients treated with anti-CGRP antibodies experienced zero migraine days — a remarkable outcome for a condition previously managed only with repurposed drugs.
What the researchers found
All four anti-CGRP monoclonal antibodies (eptinezumab, fremanezumab, galcanezumab, and erenumab) proved effective, tolerable, and safe for migraine prevention in phase II clinical trials. Mean monthly migraine day reductions ranged from 3.4 to 6.3 days after 8-12 weeks of treatment, with placebo-subtracted benefit of 1 to 2.18 days. Up to 32% of patients achieved total migraine freedom. No substance class-specific adverse events or treatment-related serious adverse events occurred. The antibodies likely act peripherally since their large size prevents blood-brain barrier penetration, revealing that peripheral CGRP signaling plays a pivotal role in migraine.
Why it matters
Anti-CGRP antibodies represent the first migraine treatments specifically developed based on understanding the disease's biology — previous preventive treatments were all repurposed from other conditions. This review captures a landmark moment in headache medicine and peptide therapeutics, documenting the clinical validation of targeting the CGRP peptide pathway. The finding that these drugs work peripherally fundamentally changed our understanding of migraine as a disease.
The numbers in context
4 mAbs reviewed · 3.4-6.3 fewer migraine days/month · placebo-subtracted benefit 1-2.18 days · up to 32% migraine freedom · 8-12 week treatment periods · CGRP is 37 amino acids · no class-specific adverse events
How the study worked
This is a narrative review summarizing the biology of CGRP, the development rationale for anti-CGRP monoclonal antibodies, and the phase II clinical trial results for all four anti-CGRP antibodies being developed for migraine prevention. It covers mechanism of action, pharmacokinetics, efficacy data, and safety profiles.
Who was studied
Review of phase II clinical trial data across episodic and chronic migraine patients
What this study cannot tell us
At the time of publication (2018), only phase II trial data were available; phase III results were still pending. Long-term safety data beyond the trial durations were unavailable. The review does not include comparative effectiveness data between the four antibodies. Potential vascular safety concerns and the impact of anti-drug antibodies remained unresolved questions.
How to read the evidence
This is a narrative review of phase II randomized controlled trial data for all four anti-CGRP antibodies. The underlying trials are high-quality, though phase III results and long-term safety data were not yet available at the time of publication.
When this study was published
Published in 2018, this review captured the anti-CGRP antibody field just before FDA approvals began (erenumab approved May 2018). Since then, all four antibodies have been approved, and extensive real-world and phase III data have confirmed the positive findings described here.
The bigger picture
This review captures a watershed moment in both migraine medicine and peptide therapeutics. Anti-CGRP antibodies validated decades of basic research into CGRP's role in migraine and proved that specifically targeting a neuropeptide could treat a neurological disease. All four antibodies have since been approved and are now widely used, transforming migraine treatment. They also demonstrated that peptide-targeted biologics could work for neurological conditions through peripheral mechanisms.
Questions still open
- How do the four anti-CGRP antibodies compare to each other in terms of efficacy and tolerability in head-to-head trials?
- What are the long-term vascular safety implications of chronically blocking CGRP, given its vasodilatory role?
- Could anti-CGRP therapy be effective for other headache disorders beyond migraine, such as cluster headache or post-traumatic headache?
Common questions
What is CGRP and why is blocking it effective for migraines?
Why is it significant that these antibodies work peripherally?
Read the original research
The Biology of Monoclonal Antibodies: Focus on Calcitonin Gene-Related Peptide for Prophylactic Migraine Therapy.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 15(2), 324-335
Citation
Raffaelli, Bianca; Reuter, Uwe. (2018). The Biology of Monoclonal Antibodies: Focus on Calcitonin Gene-Related Peptide for Prophylactic Migraine Therapy.. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 15(2), 324-335. https://doi.org/10.1007/s13311-018-0622-7