CXCR4 Inhibitors
4 drugsAbout CXCR4
CXCR4, or C-X-C chemokine receptor type 4, is a chemokine receptor involved in cell migration, adhesion, and survival. It plays a crucial role in various biological processes, making it a compelling target for therapeutic intervention.
Human genetics provide strong validation for CXCR4 as a therapeutic target, with a max genetic score of 0.92. Loss-of-function variants are associated with WHIM syndrome 1 (score 0.92) and skin neoplasm (score 0.68), suggesting activation may be beneficial.
CXCR4 is targeted by four FDA-approved small molecule drugs: APHEXDA, PLERIXAFOR, MOZOBIL, and XOLREMDI. These drugs are utilized in oncology (3 drugs) and other therapeutic areas.
CXCR4 Genetic Evidence Strong
CXCR4 has strong genetic support with a max score of 0.92 linked to WHIM syndrome 1.
Strong genetic support suggests CXCR4 agonists have a higher probability of clinical success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in genetic, familial or congenital disease, hematologic disease, immune system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
14 totalGWAS and other genetic studies link CXCR4 to 14 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for CXCR4 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 CXCR4 Drugs
Four companies have approved CXCR4-targeting drugs, including AYRMID PHARMA, EUGIA PHARMA, Sanofi, and X4 PHARMS.
The competitive landscape is moderately fragmented, suggesting relatively low barriers to entry.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| PLERIXAFOR | Teva | 2023 | 2 |
CXCR4 Drug Modality Landscape
Modalities
Routes of Administration
CXCR4 is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape suggests an opportunity for non-small molecule CXCR4-targeting therapies.
CXCR4 Clinical Trials 122 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on CXCR4. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 64 | 39 | 12 | 13 | 76% |
| Phase 2 | 48 | 28 | 9 | 11 | 76% |
| Phase 3 | 6 | 4 | 1 | 1 | 80% |
| Phase 4 | 4 | 3 | 0 | 1 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved CXCR4 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting CXCR4. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
CXCR4 Drug Approval Timeline (2008 - 2024)
The first CXCR4-targeting drug was approved in 2008, and the most recent in 2024.
The approval timeline shows continued interest in CXCR4, with recent approvals indicating market viability.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 65 (9 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 CXCR4. A trial counts if an approved drug acting on CXCR4 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.