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).
Calcineurin 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 Calcineurin 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 |
|---|---|---|---|
| ASTAGRAF XL | ASTELLAS | 2013 | 1 |
| ENVARSUS XR | VELOXIS PHARMS INC | 2015 | 1 |
| PIMECROLIMUS | GLENMARK PHARMS LTD | 2018 | 1 |
| VEVYE | HARROW EYE | 2023 | 1 |
| PROTOPIC | LEO PHARMA AS | 2000 | 1 |
| LUPKYNIS | AURINIA | 2021 | 1 |
| TACROLIMUS | Viatris | 2009 | - |
Calcineurin 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.
Calcineurin Clinical Trials 812 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Calcineurin. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 166 | 111 | 27 | 26 | 80% |
| Phase 2 | 325 | 163 | 66 | 95 | 71% |
| Phase 3 | 122 | 72 | 26 | 24 | 73% |
| Phase 4 | 199 | 146 | 22 | 31 | 87% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
5 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.
Calcineurin 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
- • Sponsors: 347 (91 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 Calcineurin. A trial counts if an approved drug acting on Calcineurin 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.