ERBB2 Inhibitors & Biosimilars
22 drugsAbout ERBB2
ERBB2 (HER2/neu) is a receptor tyrosine kinase crucial for cell growth, proliferation, and differentiation. It plays a key role in signaling pathways that regulate tissue development and is often overexpressed in cancer.
Human genetics provide strong validation of ERBB2 as a therapeutic target, with variants linked to hyperphosphatasia-intellectual disability syndrome (score 0.77) and colorectal cancer (score 0.74). Loss-of-function variants are associated with increased risk of colorectal cancer, suggesting inhibition is beneficial.
ERBB2 is targeted by 22 FDA-approved drugs, including ENHERTU, TAGRISSO, and OGIVRI, across biologics (10), small molecules (8), ADCs (2), and antibodies (2). Oncology accounts for 18 approved drugs, with the remaining 4 targeting other therapeutic areas.
ERBB2 Genetic Evidence Strong
ERBB2 has strong genetic support with a max score of 0.77 linking it to hyperphosphatasia-intellectual disability syndrome.
Strong genetic support increases the likelihood of clinical success, making ERBB2 a promising target for further drug development.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 50% directional consistency across 2 traits
- • Strong signal in gastrointestinal disease, cancer or benign tumor, respiratory or thoracic disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
50% alignedEvidence Across Diseases
11 totalGWAS and other genetic studies link ERBB2 to 11 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for ERBB2 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 ERBB2 Drugs
Sixteen companies have approved drugs targeting ERBB2, with Viatris, CELLTRION INC, and DAIICHI SANKYO among the top players.
The presence of multiple companies indicates a competitive market, requiring differentiation strategies for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TRAZIMERA | Pfizer | 2019 | 3 |
| KANJINTI | Amgen | 2019 | 3 |
| HERCEPTIN | Roche | 1998 | 3 |
| OGIVRI | Viatris | 2017 | 3 |
| ONTRUZANT | SAMSUNG BIOEPIS CO LTD | 2019 | 3 |
| PHESGO | Roche | 2020 | 2 |
| PERJETA | Roche | 2012 | 2 |
| BIZENGRI | MERUS N.V. | 2024 | 2 |
| TUKYSA | SEAGEN | 2020 | 2 |
| NERLYNX | PUMA BIOTECH | 2017 | 1 |
| HYRNUO | Bayer | 2025 | 1 |
| VIZIMPRO | Pfizer | 2018 | 1 |
| MARGENZA | TERSERA THERAPEUTICS LLC | 2020 | 1 |
| HERCEPTIN HYLECTA | Roche | 2019 | 1 |
| TYKERB | Novartis | 2007 | 1 |
| KADCYLA | Roche | 2013 | 1 |
| GILOTRIF | Boehringer Ingelheim | 2013 | 1 |
| HERNEXEOS | Boehringer Ingelheim | 2025 | 1 |
| ZIIHERA | JAZZ PHARMS | 2024 | 1 |
ERBB2 Drug Modality Landscape
Modalities
Routes of Administration
ERBB2 is druggable by both biologics (14) and small molecules (7), indicating broad therapeutic accessibility.
The relatively low number of ADCs and antibodies suggests a potential whitespace opportunity for novel modalities targeting ERBB2.
📈 Modality Evolution
Antibodies pioneered ERBB2 targeting (1998), with other biologics entering more recently (2017).
ERBB2 Clinical Trials 1,347 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on ERBB2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 399 | 205 | 69 | 122 | 75% |
| Phase 2 | 697 | 244 | 107 | 344 | 70% |
| Phase 3 | 224 | 95 | 18 | 111 | 84% |
| Phase 4 | 27 | 10 | 2 | 15 | 83% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved ERBB2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting ERBB2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
ERBB2 Drug Approval Timeline (1998 - 2025)
Unresectable or metastatic HER2-positive breast cancer
The first ERBB2-targeted drug, HERCEPTIN, was approved in 1998, with the most recent, HYRNUO, approved in 2025.
The 28-year span of approvals suggests continued innovation and market potential for ERBB2-targeted therapies.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 16 companies competing
- • Market share by company
Full Drug Portfolio
- • All 22 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 22-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 457 (146 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 ERBB2. A trial counts if an approved drug acting on ERBB2 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.