CRAF Inhibitors
3 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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Glioma with only 3 trials.
- phase1 represents biological uncertainty with 57% completion.
Human 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 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 Modality Landscape
Modalities
Routes of Administration
CRAF is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like PROTACs or biologics could provide a competitive advantage.
Clinical Trials 256 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 95 | 53 | 28 | 12 | 65% |
| Phase 2 | 123 | 44 | 30 | 49 | 59% |
| Phase 3 | 28 | 18 | 2 | 8 | 90% |
| Phase 4 | 10 | 4 | 2 | 3 | 67% |
Top Sponsors
By Modality
Phase 3 Readout Calendar Pro
3 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.
Drug Approval Timeline (2011 - 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
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-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 143 clinical trials targeting CRAF.
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