M5 Inhibitors
5 drugsAbout M5
The M5 receptor, a member of the muscarinic acetylcholine receptor family (mAChRs), binds acetylcholine to mediate various physiological processes. It plays a crucial role in neurotransmission and cellular signaling pathways within the central nervous system.
Human genetic studies provide moderate support for M5 as a therapeutic target (max score 0.48), with variants linked to Sjogren syndrome. While the genetic evidence is not strong, existing M5-targeting drugs demonstrate therapeutic potential.
M5 is targeted by five FDA-approved small molecule drugs, including INCRUSE ELLIPTA, SPIRIVA RESPIMAT, and YUPELRI. Four of these drugs are used in respiratory medicine, while one addresses a different therapeutic area.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Bladder Cancer with only 1 trials.
Human Genetic Evidence Moderate
Genetic evidence offers moderate support for M5, with a top score of 0.48 linked to Sjogren syndrome.
Further research is needed to validate M5 as a drug target, potentially focusing on indications with stronger genetic links.
Evidence Across Diseases
17 totalGWAS and other genetic studies link CHRM5 to 17 diseases.
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 Drugs
Five companies have approved drugs targeting M5, including GSK, Boehringer Ingelheim and Viatris.
The presence of multiple players suggests a competitive market, requiring differentiated strategies for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TUDORZA PRESSAIR | AZURITY | 2012 | 1 |
| INCRUSE ELLIPTA | GSK | 2014 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
M5 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage in targeting M5.
Clinical Trials 283 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 45 | 37 | 1 | 7 | 97% |
| Phase 2 | 57 | 46 | 6 | 5 | 88% |
| Phase 3 | 120 | 109 | 4 | 7 | 96% |
| Phase 4 | 61 | 51 | 8 | 2 | 86% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (2012 - 2023)
The first M5-targeting drug was approved in 2012, with the most recent approval in 2018.
The relatively short approval span suggests a maturing market, potentially indicating limited whitespace for new M5-targeting drugs.
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Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-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 M5.
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