BRAF V600E Inhibitors
4 drugsAbout BRAF V600E
BRAF V600E is a mutated form of the BRAF protein, a serine/threonine kinase in the RAS/MAPK pathway that regulates cell growth and differentiation. The V600E mutation constitutively activates the kinase, driving uncontrolled cell proliferation.
Human genetics strongly supports BRAF as a target (max score 0.96), with variants linked to rasopathy (0.96) and cardiofaciocutaneous syndromes (0.94). Inhibition is likely beneficial based on genetic evidence.
Four FDA-approved small molecule drugs target BRAF V600E: OJEMDA, STIVARGA, TAFINLAR, and ZELBORAF. These drugs are developed by DAY ONE BIOPHARMS, Bayer, Novartis and Roche, and span oncology and other therapeutic areas.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Clinical Stage IV Cutaneous Melanoma AJCC v8 with only 4 trials.
BRAF V600E Genetic Evidence Strong
Strong genetic evidence (score 0.96) links BRAF V600E to multiple diseases.
High genetic support suggests BRAF V600E programs have increased probability of clinical success.
💡 Why inhibition?
- • Gain-of-function variants increase disease risk — blocking overactivity may help
- • 100% directional consistency across 1 traits
- • Strong signal in genetic, familial or congenital disease, integumentary system disease, cardiovascular disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link BRAF to 28 diseases.
Gain-of-function causes disease; inhibition may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for BRAF 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 BRAF V600E Drugs
Four companies have approved BRAF V600E-targeting drugs.
The BRAF V600E market has moderate competition, requiring strong differentiation for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| OJEMDA | DAY ONE BIOPHARMS | 2024 | 1 |
BRAF V600E Drug Modality Landscape
Modalities
Routes of Administration
BRAF V600E is amenable to small molecule drugs, with oral options available for convenient dosing.
Consider exploring alternative modalities to differentiate from existing BRAF V600E therapies.
BRAF V600E Clinical Trials 431 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 143 | 79 | 37 | 24 | 68% |
| Phase 2 | 233 | 86 | 48 | 98 | 64% |
| Phase 3 | 45 | 23 | 8 | 14 | 74% |
| Phase 4 | 10 | 5 | 2 | 3 | 71% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
7 Phase 3 trials testing approved BRAF V600E drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting BRAF V600E. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
BRAF V600E Drug Approval Timeline (2011 - 2024)
The first BRAF V600E inhibitor was approved in 2011, with the most recent in 2024.
The continued approval of BRAF V600E inhibitors suggests sustained interest and potential for further innovation.
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: 6 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 350 clinical trials targeting BRAF V600E.
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