CGRP Inhibitors
3 drugsAbout CGRP
CGRP (Calcitonin Gene-Related Peptide) is a neuropeptide that transmits signals between neurons and plays a role in various physiological processes, particularly within the central nervous system (CNS).
Human genetic studies provide strong validation for CGRP (encoded by CALCA) as a therapeutic target, with variants linked to migraine disorder (score 0.75), COVID-19 (0.56) and diverticular disease (0.44). Loss-of-function variants are protective against migraine, supporting inhibition-based therapies.
CGRP is targeted by 3 FDA-approved biologic drugs including EMGALITY, AJOVY, and VYEPTI, all indicated for CNS disorders. These drugs have been developed by Eli Lilly, Teva, and Lundbeck Seattle BioPharmaceuticals, Inc.
CGRP Genetic Evidence Strong
Genetic evidence strongly supports CGRP as a drug target, with a maximum score of 0.75 for migraine disorder.
Strong genetic support suggests a higher likelihood of clinical success, potentially justifying investment in CGRP-targeting therapies for migraine.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 1 traits
- • Strong signal in nervous system disease, cardiovascular disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
4 totalGWAS and other genetic studies link CALCA to 4 diseases.
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for CALCA colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top CGRP Drugs
The CGRP drug market is concentrated among three companies: Eli Lilly, Teva, and Lundbeck Seattle BioPharmaceuticals, Inc.
High market concentration suggests potential entry barriers, requiring differentiated strategies for new entrants targeting CGRP.
CGRP Drug Modality Landscape
Modalities
Routes of Administration
CGRP requires biologic approaches (biologic (other)), likely due to its structure or location.
The absence of small molecule or antibody drugs targeting CGRP may represent a whitespace opportunity for novel therapeutic modalities.
CGRP Clinical Trials 72 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on CGRP. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 9 | 8 | 0 | 1 | 100% |
| Phase 2 | 8 | 4 | 4 | 0 | 50% |
| Phase 3 | 38 | 27 | 3 | 8 | 90% |
| Phase 4 | 17 | 10 | 3 | 4 | 77% |
Top Sponsors
By Modality
Top Conditions
CGRP Drug Approval Timeline (2018 - 2020)
The first CGRP-targeting drug was approved in 2018 (EMGALITY), with the most recent approval in 2020 (VYEPTI).
The recent approval timeline suggests a growing interest in CGRP as a therapeutic target, but may also indicate approaching market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 22 (8 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on CGRP. A trial counts if an approved drug acting on CGRP is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.