M3 Inhibitors
9 drugsAbout M3
The M3 muscarinic acetylcholine receptor (M3) mediates smooth muscle contraction and glandular secretion upon activation by acetylcholine. As a G protein-coupled receptor, it plays a crucial role in various physiological processes.
Human genetic studies provide strong validation for M3 as a therapeutic target (max score 0.75). Loss-of-function variants are associated with prune belly syndrome (score 0.75), suggesting activation may be beneficial.
M3 is targeted by 6 FDA-approved small molecule drugs, including INCRUSE ELLIPTA and SPIRIVA RESPIMAT. These drugs primarily address respiratory ailments, though one targets a different therapeutic area.
M3 Genetic Evidence Strong
CHRM3 has strong genetic support with a max score of 0.75 linked to prune belly syndrome.
Strong genetic support suggests that clinical trials targeting M3 have an increased chance of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in genetic, familial or congenital disease, urinary system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link CHRM3 to 25 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 1 strong
max H4: 1.00eQTL/pQTL signals for CHRM3 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 M3 Drugs
Five companies have approved drugs targeting M3, including GSK and Boehringer Ingelheim.
The presence of multiple established players suggests a moderately competitive market.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| SPIRIVA RESPIMAT | Boehringer Ingelheim | 2014 | 2 |
| DUAKLIR PRESSAIR | AZURITY | 2019 | 1 |
| YUPELRI | Viatris | 2018 | 1 |
| TUDORZA PRESSAIR | AZURITY | 2012 | 1 |
| BEVESPI AEROSPHERE | AstraZeneca | 2016 | 1 |
| INCRUSE ELLIPTA | GSK | 2014 | 1 |
M3 Drug Modality Landscape
Modalities
Routes of Administration
M3 is druggable by small molecules, though no oral formulations are currently approved.
The exclusive use of small molecules indicates a potential opportunity for biologics or other modalities.
M3 Clinical Trials 312 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on M3. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 39 | 34 | 4 | 1 | 89% |
| Phase 2 | 72 | 62 | 8 | 2 | 89% |
| Phase 3 | 103 | 96 | 4 | 3 | 96% |
| Phase 4 | 98 | 78 | 14 | 6 | 85% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved M3 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting M3. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
M3 Drug Approval Timeline (2012 - 2023)
The first M3-targeting drug was approved in 2012, with the most recent approval in 2019.
The relatively short approval span suggests the target is not yet saturated, with room for innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 7 companies competing
- • Market share by company
Full Drug Portfolio
- • All 9 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 9-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 103 (40 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 M3. A trial counts if an approved drug acting on M3 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.