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).
TRKB 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 TRKB 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.
TRKB 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.
TRKB Clinical Trials 324 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on TRKB. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 94 | 42 | 14 | 38 | 75% |
| Phase 2 | 182 | 60 | 26 | 93 | 70% |
| Phase 3 | 37 | 5 | 4 | 28 | 56% |
| Phase 4 | 11 | 3 | 0 | 8 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
5 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.
TRKB 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
- • 7 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
- • Sponsors: 138 (27 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 TRKB. A trial counts if an approved drug acting on TRKB 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.