CGRP receptor Inhibitors
5 drugsAbout CGRP receptor
The CGRP receptor, a heterodimeric GPCR composed of CLR and RAMP1, is activated by the neuropeptide CGRP. This activation is implicated in physiological processes, notably migraine pathophysiology. It has emerged as a critical drug target, especially for CNS disorders.
Human genetic studies provide strong validation for CALCRL (score 0.74), a subunit of the CGRP receptor, as a therapeutic target. Genetic associations include hypertension (score 0.74) and obesity (score 0.69). Activation of the receptor is likely beneficial based on genetic evidence.
The CGRP receptor is targeted by 5 FDA-approved drugs, including AIMOVIG, ZAVZPRET, UBRELVY, QULIPTA, and NURTEC ODT, all for CNS indications. These drugs are primarily small molecules (4 drugs) and biologics (1 drug).
CGRP receptor Genetic Evidence Strong
Genetic evidence strongly supports the CGRP receptor as a target, with a max score of 0.74.
Strong genetic support suggests a higher probability of clinical success for CGRP-targeting therapies.
💡 Why activation?
- • Gain-of-function variants reduce disease risk — enhancing activity may help
- • 100% directional consistency across 1 traits
- • Strong signal in nutritional or metabolic disease, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link CALCRL to 39 diseases.
Activating this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for CALCRL 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 receptor Drugs
Amgen, Pfizer, and AbbVie are the key players in the CGRP receptor drug market.
High market concentration suggests significant barriers to entry for new companies.
CGRP receptor Drug Modality Landscape
Modalities
Routes of Administration
CGRP receptor is druggable by both biologics (1) and small molecules (4), indicating broad therapeutic accessibility.
Consider exploring novel biologic modalities to differentiate from existing small molecule therapies.
📈 Modality Evolution
other biologics pioneered CGRP receptor targeting (2018), with small molecules entering more recently (2019).
CGRP receptor Clinical Trials 116 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on CGRP receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 17 | 11 | 2 | 4 | 85% |
| Phase 2 | 27 | 15 | 4 | 8 | 79% |
| Phase 3 | 45 | 30 | 3 | 12 | 91% |
| Phase 4 | 27 | 16 | 4 | 7 | 80% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
4 Phase 3 trials testing approved CGRP receptor drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting CGRP receptor. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
CGRP receptor Drug Approval Timeline (2018 - 2023)
The first CGRP receptor drug was approved in 2018, with the most recent in 2023.
The recent approval suggests continued interest and potential for further development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 30 (7 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 receptor. A trial counts if an approved drug acting on CGRP receptor 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.