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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Chronic Migraine in Children with only 1 trials.
- phase2 represents biological uncertainty with 50% completion.
Human 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 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.
Drug Modality Landscape
Modalities
Routes of Administration
CGRP is druggable by both biologics (4) and small molecules (4), indicating broad therapeutic accessibility.
The absence of small molecule or antibody drugs targeting CGRP may represent a whitespace opportunity for novel therapeutic modalities.
📈 Modality Evolution
other biologics pioneered CGRP targeting (2018), with small molecules entering more recently (2019).
Clinical Trials 80 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 16 | 15 | 0 | 1 | 100% |
| Phase 2 | 9 | 5 | 4 | 0 | 56% |
| Phase 3 | 39 | 29 | 3 | 7 | 91% |
| Phase 4 | 16 | 9 | 4 | 3 | 69% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
6 Phase 3 trials testing approved CGRP drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting CGRP. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Drug Approval Timeline (2018 - 2023)
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
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 72 clinical trials targeting CGRP.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities