Mannose-6-phosphate receptor Inhibitors
4 drugsAbout Mannose-6-phosphate receptor
The Mannose-6-phosphate receptor (M6PR) traffics lysosomal enzymes within cells by binding to mannose-6-phosphate (M6P) tagged proteins, directing them to the lysosome for degradation. This receptor is crucial for proper lysosomal function and cellular recycling processes.
Human genetic studies provide strong validation for targeting IGF2R (M6PR), with variants linked to coronary artery disease (score 0.84) and hypercholesterolemia (score 0.74). These genetic associations support therapeutic interventions modulating M6PR activity.
Four FDA-approved biologic drugs target the M6PR pathway, including VIMIZIM, NAGLAZYME, ALDURAZYME, and LAMZEDE. These drugs are used in therapeutic areas beyond common diseases, highlighting the receptor's importance in treating a range of conditions.
Mannose-6-phosphate receptor Genetic Evidence Strong
Genetic evidence strongly supports IGF2R (M6PR) as a drug target, with a max score of 0.84 linked to coronary artery disease.
Strong genetic support suggests a higher likelihood of clinical success for M6PR-targeting therapies.
Evidence Across Diseases
20 totalGWAS and other genetic studies link IGF2R to 30 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for IGF2R 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 Mannose-6-phosphate receptor Drugs
Three companies, including BIOMARIN and CHIESI FARMACEUTICI SPA, have approved drugs targeting M6PR.
The concentrated market suggests high barriers to entry for new companies developing M6PR-targeting drugs.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| LAMZEDE | CHIESI FARMACEUTICI SPA | 2023 | 1 |
Mannose-6-phosphate receptor Drug Modality Landscape
Modalities
Routes of Administration
Mannose-6-phosphate receptor requires biologic approaches (enzyme), likely due to its structure or location.
The absence of small molecule or antibody drugs indicates a whitespace opportunity for novel modalities.
Mannose-6-phosphate receptor Clinical Trials 9 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Mannose-6-phosphate receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 5 | 3 | 1 | 1 | 75% |
| Phase 3 | 2 | 1 | 1 | 0 | 50% |
| Phase 4 | 2 | 1 | 1 | 0 | 50% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Mannose-6-phosphate receptor Drug Approval Timeline (2003 - 2023)
The first drug targeting M6PR was approved in 2003, with the most recent approval in 2023.
The 21-year span indicates a sustained interest in M6PR as a drug target, but potential saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 6 (3 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 Mannose-6-phosphate receptor. A trial counts if an approved drug acting on Mannose-6-phosphate receptor 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.