PIK3CA Inhibitors
3 drugsAbout PIK3CA
PIK3CA, also known as PI3Kα, is a lipid kinase enzyme crucial in the PI3K/AKT/mTOR pathway, regulating cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway is common across diseases.
Human genetics strongly support PIK3CA as a drug target (max score 0.96), with variants linked to conditions like megalencephaly and breast cancer (score 0.92). Loss-of-function variants are protective in breast cancer, suggesting inhibition is beneficial.
Two FDA-approved small molecule drugs, VIJOICE and PIQRAY, target PIK3CA, both developed by Novartis. Applications span oncology and other therapeutic areas.
PIK3CA Genetic Evidence Strong
PIK3CA has strong genetic support with a maximum score of 0.96 across 31 diseases.
The strong genetic support suggests a higher probability of clinical trial success for PIK3CA-targeting drugs.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 1 traits
- • Strong signal in integumentary system disease, reproductive system or breast 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 PIK3CA to 31 diseases.
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PIK3CA 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 PIK3CA Drugs
Novartis is the only company with approved PIK3CA-targeting drugs.
The market is highly concentrated, presenting a barrier to entry for new companies.
PIK3CA Drug Modality Landscape
Modalities
Routes of Administration
PIK3CA 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.
PIK3CA Clinical Trials 92 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on PIK3CA. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 27 | 8 | 3 | 16 | 73% |
| Phase 2 | 52 | 6 | 10 | 36 | 38% |
| Phase 3 | 12 | 1 | 4 | 7 | 20% |
| Phase 4 | 1 | 1 | 0 | 0 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
4 Phase 3 trials testing approved PIK3CA drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting PIK3CA. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
PIK3CA Drug Approval Timeline (2019 - 2024)
The first PIK3CA-targeting drug was approved in 2019, with the most recent in 2022.
The recent approval suggests continued interest, but saturation may occur soon.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 43 (10 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 PIK3CA. A trial counts if an approved drug acting on PIK3CA 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.