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.
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 |
|---|---|---|---|
| ATORVALIQ | CMP DEV LLC | 2023 | 11 |
| FLOLIPID | SALERNO PHARMS | 2016 | 9 |
| CADUET | PHARMACIA | 2004 | 9 |
| ROSUVASTATIN CALCIUM | ACCORD HLTHCARE | 2016 | 6 |
| VYTORIN | Merck | 2004 | 6 |
| CRESTOR | AstraZeneca | 2003 | 6 |
| AMLODIPINE BESYLATE AND ATORVASTATIN CALCIUM | Apotex | 2013 | 4 |
| FLUVASTATIN SODIUM | PHARMOBEDIENT | 2012 | 4 |
| LESCOL XL | Novartis | 2000 | 4 |
| PITAVASTATIN CALCIUM | SAWAI USA | 2016 | 2 |
| LIVALO | KOWA CO | 2009 | 2 |
| ZYPITAMAG | MEDICURE | 2017 | 1 |
| PRAVASTATIN SODIUM | Dr. Reddy's | 2006 | - |
| ATORVASTATIN CALCIUM | CHARTWELL RX | 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 1,224 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on HMGCR. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 459 | 392 | 21 | 45 | 95% |
| Phase 2 | 238 | 167 | 33 | 37 | 84% |
| Phase 3 | 228 | 156 | 38 | 34 | 80% |
| Phase 4 | 299 | 213 | 37 | 49 | 85% |
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)
Therapy with lipid-altering agents should be only one com...
Atorvastatin calcium tablets are indicated: To reduce the...
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
- • 16 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
- • Sponsors: 569 (175 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 HMGCR. A trial counts if an approved drug acting on HMGCR 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.