SMN2 Inhibitors
2 drugsAbout SMN2
SMN2 (Survival Motor Neuron 2) is a paralog of SMN1 that produces a truncated protein. Modulating SMN2 expression can compensate for deficiencies in SMN1, making it a therapeutic target.
SMN2 is strongly supported by genetics (max score 0.89) with variants linked to spinal muscular atrophy. Loss-of-function variants increase disease risk, supporting therapies that enhance SMN2 function.
SMN2 is targeted by two FDA-approved small molecule drugs: SPINRAZA (Biogen) and EVRYSDI (Roche). These drugs address rare diseases where SMN protein levels are insufficient.
SMN2 Genetic Evidence Strong
SMN2 has strong genetic support with a maximum score of 0.89.
Strong genetic support suggests a higher likelihood of clinical trial success.
Evidence Across Diseases
7 totalGWAS and other genetic studies link SMN2 to 7 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for SMN2 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 SMN2 Drugs
The competitive landscape is concentrated with Biogen and Roche holding all approved drugs.
High market concentration indicates potential entry barriers for new companies.
SMN2 Drug Modality Landscape
Modalities
Routes of Administration
SMN2 is amenable to small molecule drugs, with oral options available for convenient dosing.
The exclusive use of small molecules suggests an opportunity for novel modalities.
SMN2 Clinical Trials 33 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on SMN2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 11 | 10 | 0 | 1 | 100% |
| Phase 2 | 10 | 7 | 1 | 2 | 88% |
| Phase 3 | 7 | 4 | 1 | 2 | 80% |
| Phase 4 | 5 | 2 | 0 | 3 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved SMN2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting SMN2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
SMN2 Drug Approval Timeline (2016 - 2020)
The approval timeline spans 5 years, with the first drug approved in 2016 and the most recent in 2020.
The recent approval suggests continued interest and potential for further development.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 2 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 2-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 6 (4 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 SMN2. A trial counts if an approved drug acting on SMN2 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.