CFTR Inhibitors
7 drugsAbout CFTR
CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is a protein involved in chloride ion transport across epithelial cell membranes. Its function is critical for maintaining fluid balance in organs such as the lungs and pancreas.
Human genetics strongly supports CFTR as a therapeutic target, with variants linked to cystic fibrosis (score 0.97) and congenital bilateral aplasia of vas deferens (score 0.98). Loss-of-function variants increase disease risk, suggesting activation strategies are likely beneficial.
CFTR is targeted by 7 FDA-approved small molecule drugs, including KALYDECO, ORKAMBI and TRIKAFTA. These drugs are primarily used for respiratory indications, though some have applications in other therapeutic areas.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Diarrhea with only 1 trials.
Human Genetic Evidence Strong
Strong genetic evidence supports CFTR's role in multiple diseases, with a maximum score of 0.98.
High genetic support suggests CFTR-targeting drugs have a higher probability of clinical success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 50% directional consistency across 2 traits
- • Strong signal in respiratory or thoracic disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
50% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link CFTR to 40 diseases.
Activating this target may be therapeutic
Effect Sizes
Genetic effect on disease risk. OR<1 or β<0 = loss-of-function is protective (inhibiting target may help).
🔗 Colocalization Evidence 20 strong
max H4: 0.96eQTL/pQTL signals for CFTR 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
Three companies have approved CFTR-targeting drugs, with Vertex Pharmaceuticals as a major player.
The market is relatively concentrated, suggesting high barriers to entry for new companies.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| ORKAMBI | Vertex Pharmaceuticals | 2015 | 1 |
| KALYDECO | Vertex Pharmaceuticals | 2012 | 1 |
| SYMDEKO (COPACKAGED) | Vertex Pharmaceuticals | 2018 | 1 |
| TRIKAFTA (COPACKAGED) | Vertex Pharmaceuticals | 2019 | - |
Drug Modality Landscape
Modalities
Routes of Administration
CFTR is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like biologics could provide a competitive advantage.
Clinical Trials 160 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 30 | 26 | 1 | 3 | 96% |
| Phase 2 | 43 | 31 | 4 | 8 | 89% |
| Phase 3 | 66 | 57 | 3 | 6 | 95% |
| Phase 4 | 21 | 11 | 6 | 3 | 65% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (2004 - 2024)
The first CFTR drug was approved in 2004, with the most recent approval in 2024.
The continued approval of new drugs indicates ongoing innovation and market potential.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 7 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 7-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 113 clinical trials targeting CFTR.
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