HER3 Inhibitors
2 drugsAbout HER3
HER3 (human epidermal growth factor receptor 3) is a receptor tyrosine kinase in the EGFR family. It has impaired kinase activity and heterodimerizes with other EGFR family members like HER2 to activate downstream signaling pathways, impacting cell growth and survival.
HER3 is a compelling oncology target due to its role in tumor growth and resistance. Human genetic studies provide strong support for ERBB3 (score 0.86), with loss-of-function variants associated with increased risk of visceral neuropathy and lethal congenital contracture syndrome.
Two HER3-targeting drugs have gained approval: TAGRISSO (AstraZeneca) and BIZENGRI (MERUS N.V.). These include one biologic and one small molecule, both used in oncology and other therapeutic areas, highlighting the potential of HER3-directed therapies.
HER3 Genetic Evidence Strong
ERBB3 has strong genetic support (score 0.86) with multiple disease associations.
Strong genetic support suggests that clinical trials targeting ERBB3 have a higher likelihood 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, gastrointestinal disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
9 totalGWAS and other genetic studies link ERBB3 to 9 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for ERBB3 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 HER3 Drugs
The HER3 drug market is led by AstraZeneca and MERUS N.V.
The presence of only two companies indicates a relatively unconcentrated market with potential for new entrants.
HER3 Drug Modality Landscape
Modalities
Routes of Administration
HER3 is druggable by both biologics (1) and small molecules (1), indicating broad therapeutic accessibility.
The balance between biologics and small molecules suggests opportunities for novel modalities like PROTACs.
📈 Modality Evolution
Small molecules pioneered HER3 targeting (2015), with other biologics entering more recently (2024).
HER3 Clinical Trials 178 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on HER3. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 61 | 17 | 9 | 35 | 65% |
| Phase 2 | 87 | 19 | 5 | 63 | 79% |
| Phase 3 | 28 | 0 | 2 | 26 | 0% |
| Phase 4 | 2 | 1 | 0 | 1 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved HER3 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting HER3. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
HER3 Drug Approval Timeline (2015 - 2024)
The first HER3-targeting drug was approved in 2015, with the most recent in 2024.
The recent approval suggests renewed interest and potential for further drug development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 2 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 2-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 110 (43 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 HER3. A trial counts if an approved drug acting on HER3 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.