Calcineurin Inhibitors
10 drugsAbout Calcineurin
Calcineurin (protein phosphatase 3, catalytic subunit alpha) is a calcium- and calmodulin-dependent serine/threonine protein phosphatase involved in cellular signaling pathways. It regulates T-cell activation, muscle development, and neuronal signaling by dephosphorylating target proteins.
Human genetic studies provide strong validation for targeting Calcineurin, with variants in PPP3CA linked to developmental and epileptic encephalopathy (score 0.93). Loss-of-function variants are associated with increased risk, suggesting activation of Calcineurin may be therapeutically beneficial.
Calcineurin is targeted by 10 FDA-approved small molecule drugs, including PROGRAF, CEQUA and VEVYE. These drugs are primarily used in 'other' therapeutic areas (7 drugs), immunology (2 drugs), and ophthalmology (1 drug).
Human Genetic Evidence Strong
Genetic evidence strongly supports Calcineurin as a drug target, with a maximum score of 0.93 for developmental and epileptic encephalopathy.
The strong genetic support increases the likelihood of clinical success, warranting further investment in Calcineurin-targeting therapies.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link PPP3CA to 34 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 17 strong
max H4: 0.98eQTL/pQTL signals for PPP3CA 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 Drugs
Nine companies have approved Calcineurin-targeting drugs, with ACCORD HLTHCARE, ASTELLAS, and Sun Pharma as key players.
The fragmented market suggests opportunities for consolidation or strategic partnerships to gain market share.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| ELIDEL | BAUSCH | 2001 | 1 |
| PROTOPIC | LEO PHARMA AS | 2000 | 1 |
| LUPKYNIS | AURINIA | 2021 | 1 |
| CEQUA | Sun Pharma | 2018 | 1 |
| ASTAGRAF XL | ASTELLAS | 2013 | 1 |
| VEVYE | HARROW EYE | 2023 | 1 |
| TACROLIMUS | GLENMARK PHARMS LTD | 2009 | - |
Drug Modality Landscape
Modalities
Routes of Administration
Calcineurin is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like biologics could provide a competitive advantage and address unmet needs.
Clinical Trials 834 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 179 | 118 | 26 | 32 | 82% |
| Phase 2 | 333 | 170 | 66 | 93 | 72% |
| Phase 3 | 125 | 77 | 25 | 23 | 75% |
| Phase 4 | 197 | 146 | 22 | 26 | 87% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
6 Phase 3 trials testing approved Calcineurin drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Calcineurin. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Drug Approval Timeline (1994 - 2023)
The first Calcineurin-targeting drug was approved in 1994 (PROGRAF), with the most recent approval in 2023 (VEVYE).
The continued approvals indicate sustained interest and potential for further innovation in Calcineurin-targeted therapies.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 9 companies competing
- • Market share by company
Full Drug Portfolio
- • All 10 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 10-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 439 clinical trials targeting Calcineurin.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities