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.
CFTR 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 CFTR 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 |
|---|---|---|---|
| SYMDEKO (COPACKAGED) | Vertex Pharmaceuticals | 2018 | 1 |
| ORKAMBI | Vertex Pharmaceuticals | 2015 | 1 |
| ALYFTREK | Vertex Pharmaceuticals | 2024 | 1 |
| TRIKAFTA (COPACKAGED) | Vertex Pharmaceuticals | 2019 | - |
CFTR 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.
CFTR Clinical Trials 75 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on CFTR. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 13 | 12 | 0 | 1 | 100% |
| Phase 2 | 25 | 19 | 2 | 4 | 90% |
| Phase 3 | 24 | 22 | 1 | 1 | 96% |
| Phase 4 | 13 | 5 | 4 | 4 | 56% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
CFTR 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
- • Sponsors: 28 (10 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 CFTR. A trial counts if an approved drug acting on CFTR 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.