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.
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 438 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on BRAF V600E. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 145 | 80 | 37 | 24 | 68% |
| Phase 2 | 236 | 90 | 50 | 96 | 64% |
| Phase 3 | 46 | 23 | 8 | 15 | 74% |
| Phase 4 | 11 | 5 | 2 | 4 | 71% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
5 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.
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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
- • Sponsors: 203 (46 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 BRAF V600E. A trial counts if an approved drug acting on BRAF V600E 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.