RET Inhibitors
14 drugsAbout RET
RET (RET Proto-Oncogene) is a receptor tyrosine kinase involved in cell growth, differentiation, and survival. It plays a crucial role in neural crest development and kidney organogenesis, activated by GDNF family ligands.
Human genetics strongly support RET as a drug target (max score 0.95), with variants linked to multiple endocrine neoplasia type 2 and hereditary neoplastic syndrome. Loss-of-function variants increase disease risk, suggesting activation may be therapeutically beneficial.
RET is targeted by 14 FDA-approved small molecule drugs including LENVIMA, CABOMETYX and RETEVMO. Four drugs are approved for oncology, while ten address other therapeutic areas, developed by 13 different companies.
RET Genetic Evidence Strong
RET has strong genetic support with a maximum score of 0.95 linking it to multiple endocrine neoplasia.
Strong genetic evidence suggests RET-activating therapies have a higher probability of clinical 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, endocrine system disease, cancer or benign tumor pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link RET to 40 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for RET 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 RET Drugs
Thirteen different companies have approved RET-targeting drugs, indicating a fragmented market.
The presence of many players suggests relatively low barriers to entry in the RET-targeting space.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| RETEVMO | Eli Lilly | 2020 | 4 |
| STIVARGA | Bayer | 2012 | 3 |
| SUNITINIB MALATE | Dr. Reddy's | 2021 | 3 |
| SORAFENIB TOSYLATE | YABAO PHARM | 2020 | 3 |
| NEXAVAR | Bayer | 2005 | 3 |
| GAVRETO | RIGEL PHARMS | 2020 | 2 |
| ICLUSIG | Takeda | 2012 | 2 |
| COMETRIQ | EXELIXIS | 2012 | 1 |
| ALECENSA | Roche | 2015 | 1 |
| CAPRELSA | Sanofi | 2011 | 1 |
| RESNIBEN | AZURITY | - | - |
RET Drug Modality Landscape
Modalities
Routes of Administration
RET is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or PROTACs could provide a competitive advantage.
RET Clinical Trials 1,446 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on RET. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 443 | 278 | 80 | 83 | 78% |
| Phase 2 | 790 | 347 | 167 | 271 | 68% |
| Phase 3 | 184 | 91 | 27 | 66 | 77% |
| Phase 4 | 29 | 17 | 3 | 9 | 85% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
7 Phase 3 trials testing approved RET drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting RET. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
RET Drug Approval Timeline (2005 - 2021)
The first RET-targeting drug was approved in 2005, with the most recent approval in 2021.
The approval timeline indicates a sustained interest in RET as a drug target over the past 17 years.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 12 companies competing
- • Market share by company
Full Drug Portfolio
- • All 14 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 14-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 489 (118 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 RET. A trial counts if an approved drug acting on RET 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.