M5 Inhibitors
6 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.
M5 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 M5 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 |
|---|---|---|---|
| SPIRIVA RESPIMAT | Boehringer Ingelheim | 2014 | 2 |
| TUDORZA PRESSAIR | AZURITY | 2012 | 1 |
| INCRUSE ELLIPTA | GSK | 2014 | 1 |
M5 Drug Modality Landscape
Modalities
Routes of Administration
M5 is druggable by small molecules, though no oral formulations are currently approved.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage in targeting M5.
M5 Clinical Trials 179 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on M5. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 19 | 17 | 1 | 1 | 94% |
| Phase 2 | 35 | 31 | 4 | 0 | 89% |
| Phase 3 | 69 | 66 | 2 | 1 | 97% |
| Phase 4 | 56 | 46 | 6 | 4 | 88% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
M5 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.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 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
- • Sponsors: 51 (27 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 M5. A trial counts if an approved drug acting on M5 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.