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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Chronic Granulomatous Disease (CGD) with only 1 trials.
- phase2 represents biological uncertainty with 50% completion.
Human 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 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 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.
Clinical Trials 137 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 71 | 45 | 12 | 14 | 79% |
| Phase 2 | 49 | 30 | 10 | 8 | 75% |
| Phase 3 | 9 | 6 | 1 | 2 | 86% |
| Phase 4 | 8 | 5 | 1 | 2 | 83% |
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.
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
- • 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 63 clinical trials targeting CXCR4.
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