CRAF Inhibitors
7 drugsAbout CRAF
CRAF (RAF1), a serine/threonine-protein kinase, participates in the MAPK/ERK signaling pathway, influencing cell growth and differentiation. Aberrant activation of this pathway is implicated in various cancers, making CRAF a target for therapeutic intervention.
Human genetic studies provide strong validation for CRAF as a therapeutic target (score 0.96), with variants linked to rasopathy and Noonan syndrome. Gain-of-function variants increase disease risk, suggesting inhibition-based therapies are likely beneficial.
CRAF is targeted by 3 FDA-approved small molecule drugs including TAFINLAR, ZELBORAF and OJEMDA, primarily in oncology. These drugs are developed by DAY ONE BIOPHARMS, Novartis and Roche.
CRAF Genetic Evidence Strong
CRAF has strong genetic support with a max score of 0.96 linked to rasopathy.
Strong genetic support increases clinical success probability and warrants investment in CRAF-targeted therapies.
💡 Why inhibition?
- • Gain-of-function variants increase disease risk — blocking overactivity may help
- • 100% directional consistency across 1 traits
- • Strong signal in cardiovascular disease, genetic, familial or congenital disease, hematologic disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
18 totalGWAS and other genetic studies link RAF1 to 18 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for RAF1 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 CRAF Drugs
DAY ONE BIOPHARMS, Novartis, and Roche are the companies with approved CRAF-targeting drugs.
The presence of three companies indicates moderate competition, but also established market entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| SORAFENIB TOSYLATE | YABAO PHARM | 2020 | 3 |
| ZELBORAF | Roche | 2011 | 2 |
| OJEMDA | DAY ONE BIOPHARMS | 2024 | 1 |
| VOXZOGO | BIOMARIN | 2021 | 1 |
CRAF Drug Modality Landscape
Modalities
Routes of Administration
CRAF is primarily targeted by small molecule modalities (86% of approved drugs).
Exploring alternative modalities like PROTACs or biologics could provide a competitive advantage.
📈 Modality Evolution
Small molecules pioneered CRAF targeting (2005), with peptides entering more recently (2021).
CRAF Clinical Trials 825 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on CRAF. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 299 | 192 | 69 | 33 | 74% |
| Phase 2 | 408 | 188 | 96 | 123 | 66% |
| Phase 3 | 102 | 59 | 18 | 25 | 77% |
| Phase 4 | 16 | 9 | 3 | 4 | 75% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
5 Phase 3 trials testing approved CRAF drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting CRAF. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
CRAF Drug Approval Timeline (2005 - 2024)
The first CRAF-targeting drug was approved in 2011, with the most recent in 2024.
The 14-year span suggests continued interest and potential for further innovation in CRAF inhibition.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 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: 348 (90 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 CRAF. A trial counts if an approved drug acting on CRAF 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.