HMGCR Inhibitors
17 drugsAbout HMGCR
HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in the mevalonate pathway for cholesterol biosynthesis. It is a validated drug target for managing cholesterol levels and preventing cardiovascular events.
HMGCR has strong genetic support as a therapeutic target (max score 0.89). Loss-of-function variants are protective against metabolic disease (score 0.89), hypercholesterolemia (0.88), and hyperlipidemia (0.85), suggesting inhibition is beneficial.
HMGCR is targeted by 17 FDA-approved small molecule drugs, including Lipitor, Crestor and Pravachol. These drugs are primarily used in cardiovascular and metabolic therapeutic areas.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Type 2 Diabetes Mellitus with only 5 trials.
HMGCR Genetic Evidence Strong
HMGCR has strong genetic support with a maximum score of 0.89.
The strong genetic support suggests a higher probability of clinical trial success for HMGCR-targeting drugs.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 3 traits
- • Strong signal in nutritional or metabolic disease, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link HMGCR to 23 diseases.
Inhibiting this target may be therapeutic
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for HMGCR 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 HMGCR Drugs
Seventeen companies have approved HMGCR-targeting drugs.
The competitive landscape suggests a fragmented market with relatively low barriers to entry for generic small molecule drugs.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| CADUET | PHARMACIA | 2004 | 10 |
| LYPQOZET | PHARMOBEDIENT | 2017 | 10 |
| SIMVASTATIN | CHARTWELL RX | 2006 | 9 |
| FLOLIPID | SALERNO PHARMS | 2016 | 9 |
| ROSUVASTATIN CALCIUM | CHARTWELL RX | 2016 | 6 |
| CRESTOR | AstraZeneca | 2003 | 6 |
| VYTORIN | Merck | 2004 | 6 |
| FLUVASTATIN SODIUM | PHARMOBEDIENT | 2012 | 4 |
| LESCOL XL | Novartis | 2000 | 4 |
| PITAVASTATIN CALCIUM | ORIENT PHARMA CO LTD | 2016 | 2 |
| LIVALO | KOWA CO | 2009 | 2 |
| ZYPITAMAG | MEDICURE | 2017 | 1 |
| PRAVASTATIN SODIUM | PHARMOBEDIENT | 2006 | - |
| ATORVASTATIN CALCIUM | INVAGEN PHARMS | 2011 | - |
HMGCR Drug Modality Landscape
Modalities
Routes of Administration
HMGCR is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide differentiation in the market.
HMGCR Clinical Trials 1,085 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 399 | 347 | 20 | 31 | 95% |
| Phase 2 | 217 | 155 | 30 | 30 | 84% |
| Phase 3 | 197 | 138 | 36 | 22 | 79% |
| Phase 4 | 272 | 195 | 32 | 44 | 86% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved HMGCR drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting HMGCR. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
HMGCR Drug Approval Timeline (1996 - 2023)
The first HMGCR-targeting drug, Lipitor, was approved in 1996, and the most recent, Atorvaliq, in 2023.
The 28-year span indicates a mature market, but recent approvals suggest continued innovation or reformulation opportunities.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 14 companies competing
- • Market share by company
Full Drug Portfolio
- • All 17 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 17-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 2 underexplored indications
- • 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 614 clinical trials targeting HMGCR.
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