TRKB Inhibitors
8 drugsAbout TRKB
TRKB (tropomyosin receptor kinase B) is a receptor tyrosine kinase crucial for neuronal survival, differentiation, and synaptic plasticity. Primarily known for its nervous system function, TRKB's involvement extends to other tissues. Activation is likely beneficial based on genetic evidence.
Human genetic studies provide strong validation for TRKB as a therapeutic target (max score 0.83). Loss-of-function variants are associated with obesity, hyperphagia, and developmental delay (score 0.83), and genetic developmental and epileptic encephalopathy (score 0.80).
TRKB is targeted by 8 FDA-approved small molecule drugs including CABOMETYX, VITRAKVI and ROZLYTREK. Applications span oncology (3 drugs) and other therapeutic areas (5 drugs).
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 82% attractiveness score.
- White space opportunity in Recurrent Malignant Solid Neoplasm with only 5 trials.
- phase3 represents biological uncertainty with 33% completion.
Human Genetic Evidence Strong
TRKB has strong genetic support with a max score of 0.83 linking it to multiple diseases.
Strong genetic support suggests that clinical trials targeting TRKB have an increased probability of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in genetic, familial or congenital disease, nervous system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
17 totalGWAS and other genetic studies link NTRK2 to 17 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
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
Eight companies have approved TRKB-targeting drugs, including Roche and EXELIXIS.
The presence of multiple companies suggests a moderately competitive landscape with potential entry barriers for new players.
Drug Modality Landscape
Modalities
Routes of Administration
TRKB is amenable to small molecule drugs, with oral options available for convenient dosing.
The exclusive use of small molecules indicates a potential whitespace opportunity for alternative modalities like antibodies or biologics.
Clinical Trials 357 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 102 | 51 | 15 | 36 | 77% |
| Phase 2 | 195 | 64 | 28 | 102 | 70% |
| Phase 3 | 43 | 9 | 5 | 29 | 64% |
| Phase 4 | 17 | 6 | 1 | 10 | 86% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
6 Phase 3 trials testing approved TRKB drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting TRKB. 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 (2012 - 2025)
The first TRKB-targeting drug was approved in 2012, with the most recent in 2025.
The continued approval of new drugs indicates sustained interest and potential for further development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 8 companies competing
- • Market share by company
Full Drug Portfolio
- • All 8 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 8-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 4 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 287 clinical trials targeting TRKB.
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