GAA Inhibitors
3 drugsAbout GAA
Glycogen debranching enzyme, also known as acid alpha-glucosidase or GAA, breaks down glycogen within lysosomes. Its deficiency leads to glycogen accumulation, particularly in muscle and liver cells.
GAA is strongly supported by human genetics (score 0.99), with loss-of-function variants in GAA linked to glycogen storage disease and cardiovascular abnormalities. Activation of GAA is likely beneficial based on genetic evidence.
Three FDA-approved drugs (POMBILITI, LUMIZYME, and MYOZYME) target GAA, all of which are biologics. These drugs are developed by Sanofi and AMICUS THERAP US.
GAA Genetic Evidence Strong
GAA has strong genetic support with a max score of 0.99 linking it to glycogen storage disease.
Strong genetic support suggests a higher probability of clinical success for GAA-targeting therapies.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in cardiovascular disease, genetic, familial or congenital disease, nutritional or metabolic disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link GAA to 20 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for GAA 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 GAA Drugs
Two companies, Sanofi and AMICUS THERAP US, have approved drugs targeting GAA.
The GAA market is relatively concentrated, potentially posing entry barriers for new competitors.
GAA Drug Modality Landscape
Modalities
Routes of Administration
GAA requires biologic approaches (enzyme), likely due to its structure or location.
The absence of small molecule drugs targeting GAA represents a potential whitespace opportunity.
GAA Clinical Trials 14 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on GAA. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 2 | 1 | 0 | 0 | 1 | - |
| Phase 3 | 4 | 2 | 0 | 2 | 100% |
| Phase 4 | 9 | 6 | 3 | 0 | 67% |
Top Sponsors
By Modality
Top Conditions
GAA Drug Approval Timeline (2006 - 2023)
The first GAA-targeting drug was approved in 2006, with the most recent approval in 2023.
The approval timeline indicates continued interest and development in GAA-targeting therapies.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 2 (2 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 GAA. A trial counts if an approved drug acting on GAA 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.