M3 Inhibitors
6 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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Bladder Cancer with only 1 trials.
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 |
|---|---|---|---|
| DUAKLIR PRESSAIR | AZURITY | 2019 | 1 |
| TUDORZA PRESSAIR | AZURITY | 2012 | 1 |
| YUPELRI | Viatris | 2018 | 1 |
M3 Drug Modality Landscape
Modalities
Routes of Administration
M3 is amenable to small molecule drugs, with oral options available for convenient dosing.
The exclusive use of small molecules indicates a potential opportunity for biologics or other modalities.
M3 Clinical Trials 174 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 19 | 17 | 0 | 2 | 100% |
| Phase 2 | 34 | 30 | 4 | 0 | 88% |
| Phase 3 | 68 | 66 | 2 | 0 | 97% |
| Phase 4 | 53 | 45 | 6 | 2 | 88% |
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
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 6 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 6-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 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 144 clinical trials targeting M3.
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