CGRP Inhibitors by Brand Name and Mechanism of Action
CGRP Monoclonal Antibodies (CGRP-mAbs)
These agents bind directly to the CGRP peptide itself, preventing it from activating its receptor and reducing free, bioavailable CGRP. 1
Ligand-Binding Monoclonal Antibodies
Fremanezumab - Humanized monoclonal antibody that directly binds to the CGRP peptide, administered subcutaneously for prevention of episodic or chronic migraine 1
Galcanezumab - Humanized monoclonal antibody that directly binds to the CGRP peptide, administered subcutaneously for migraine prevention 1
Eptinezumab (Brand: VYEPTI) - Humanized IgG1 monoclonal antibody that binds to CGRP ligand and blocks its binding to the receptor, administered intravenously every 3 months, with approximate molecular weight of 143 kD 2
Receptor-Binding Monoclonal Antibody
- Erenumab (Brand: AIMOVIG) - Human IgG2 monoclonal antibody that binds to the CGRP receptor itself (not the peptide), antagonizing CGRP receptor function, administered subcutaneously at 70 mg or 140 mg monthly 3
- Critical distinction: Erenumab works by blocking receptor activation rather than reducing the peptide 1
- Has been associated with risk for development or worsening of hypertension in post-marketing studies, unlike the ligand-binding antibodies 4, 1
- Uses a remarkable 21-residue-long CDR-H3 loop that projects into the deep interface between CLR and RAMP1 subunits 5
CGRP Receptor Antagonists (Gepants)
These are oral small-molecule drugs that competitively block the CGRP receptor without affecting CGRP peptide levels. 1
For Migraine Prevention
Atogepant - Oral CGRP receptor antagonist taken daily for episodic migraine prevention 6, 1
Rimegepant - Oral CGRP receptor antagonist taken 75 mg every other day for preventive treatment of episodic migraine 1, 7
For Acute Migraine Treatment
Rimegepant - Also approved for acute treatment of migraine attacks 6
Ubrogepant - Oral CGRP receptor antagonist for acute episodic migraine treatment 6
Zavegepant - Oral CGRP receptor antagonist for acute episodic migraine treatment 6
Key Mechanistic Differences
The fundamental distinction is between agents that neutralize the CGRP peptide versus those that block its receptor: 1
Ligand-binding mAbs (fremanezumab, galcanezumab, eptinezumab) reduce the amount of free CGRP available to activate receptors 1
Receptor-binding mAb (erenumab) prevents CGRP from activating its receptor by occupying the receptor binding site 3
Gepants (atogepant, rimegepant, ubrogepant, zavegepant) competitively antagonize the CGRP receptor through small-molecule blockade 1
Clinical Efficacy Comparison
All CGRP-targeting therapies show similar efficacy in reducing monthly migraine days by approximately 0.8-2.3 days compared to placebo 1
CGRP-mAbs may reduce migraine frequency by 0.80 fewer days per month compared to topiramate (low-certainty evidence) 6
CGRP-mAbs may reduce migraine frequency by 0.76 fewer days per month compared to valproate (low-certainty evidence) 6
No direct comparative evidence shows superiority of one CGRP-mAb over another 4
Administration Routes
Subcutaneous injection (monthly): Erenumab, fremanezumab, galcanezumab 6, 1
Intravenous infusion (every 3 months): Eptinezumab 2
Oral (daily or every other day): Atogepant, rimegepant, ubrogepant, zavegepant 6, 1
Patients generally prefer oral treatments over injectables (moderate-certainty evidence) 6, 4
Cost Considerations
Annual costs for CGRP-mAbs and gepants range from $7,071 to $22,790, substantially higher than traditional preventive medications (metoprolol $123, propranolol $393, amitriptyline $67) 6, 7