Amyloid beta Inhibitors
4 drugsAbout Amyloid beta
Amyloid beta (Aβ) is a protein fragment that forms amyloid plaques in the brain, a hallmark of Alzheimer's disease. While its precise function is still under investigation, Aβ's role in plaque formation is well-documented.
Human genetic studies provide strong validation for APP (amyloid precursor protein) as a therapeutic target in Alzheimer's disease (score 0.95). Loss-of-function variants are protective against Alzheimer's disease (score 0.87), supporting inhibition-based therapies.
Four FDA-approved drugs target amyloid beta, including KISUNLA, LEQEMBI, VIZAMYL, and LEQEMBI IQLIK. These drugs are biologics (75%) and small molecules (25%) indicated for CNS and other conditions.
Amyloid beta Genetic Evidence Strong
APP has strong genetic support with a max score of 0.95 linking it to Alzheimer's disease.
Strong genetic support increases the probability of clinical success for APP-targeting drugs.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 50% directional consistency across 2 traits
- • Strong signal in psychiatric disorder, nervous system disease, phenotype pathways
Cross-Disease Effects
Trade-off: HighDirection of Effect
50% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link APP to 34 diseases.
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for APP 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 Amyloid beta Drugs
Three companies, GE HEALTHCARE, Eli Lilly, and EISAI INC, have approved drugs targeting amyloid beta.
High market concentration suggests significant barriers to entry for new amyloid beta drugs.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| LEQEMBI IQLIK | EISAI INC | 2025 | 1 |
Amyloid beta Drug Modality Landscape
Modalities
Routes of Administration
Amyloid beta is druggable by both biologics (3) and small molecules (1), indicating broad therapeutic accessibility.
Consider developing small molecule Aβ inhibitors to differentiate from existing biologic therapies.
📈 Modality Evolution
Small molecules pioneered Amyloid beta targeting (2013), with other biologics entering more recently (2023).
Amyloid beta Clinical Trials 32 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Amyloid beta. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 4 | 4 | 0 | 0 | 100% |
| Phase 2 | 12 | 4 | 0 | 8 | 100% |
| Phase 3 | 12 | 1 | 1 | 10 | 50% |
| Phase 4 | 4 | 0 | 0 | 4 | - |
Top Sponsors
By Modality
Top Conditions
Amyloid beta Drug Approval Timeline (2013 - 2025)
The first drug was approved in 2013, and the most recent in 2025, spanning 13 years.
The recent approval suggests renewed interest, but also increasing competition in the amyloid beta space.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 13 (3 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 Amyloid beta. A trial counts if an approved drug acting on Amyloid beta 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.