GABA-T Inhibitors
5 drugsAbout GABA-T
Gamma-aminobutyric acid transaminase (GABA-T) regulates the neurotransmitter GABA in the brain, which helps calm nerve activity. GABA-T breaks down GABA, lowering its concentration between nerve cells. Inhibiting GABA-T increases GABA levels, leading to a calming effect.
Human genetic studies provide strong validation for GABA-T as a therapeutic target, with variants linked to gamma-aminobutyric acid transaminase deficiency (score 0.85). Loss-of-function variants are associated with increased disease risk, suggesting activation may be beneficial.
GABA-T is targeted by 5 FDA-approved small molecule drugs, including Vigabatrin, Vigadrone, Sabril, Vigpoder and Vigafyde. These drugs are approved for other therapeutic areas, suggesting the potential of GABA-T as a drug target.
GABA-T Genetic Evidence Strong
GABA-T has strong genetic support with a maximum score of 0.85 linked to GABA deficiency.
Strong genetic support suggests a higher probability of clinical success for GABA-T targeted 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 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 ABAT to 23 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
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 GABA-T Drugs
Four companies have approved GABA-T targeting drugs: PH Health, Aucta, Lundbeck Pharms LLC, and Pyros Pharms.
The presence of four companies suggests moderate competition, but also potential barriers to entry.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| VIGPODER | PYROS PHARMS | 2022 | 2 |
| VIGAFYDE | PYROS PHARMS | 2024 | 1 |
GABA-T Drug Modality Landscape
Modalities
Routes of Administration
GABA-T is amenable to small molecule drugs, with oral options available for convenient dosing.
The exclusive use of small molecules indicates a whitespace opportunity for exploring other modalities.
GABA-T Clinical Trials 18 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on GABA-T. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 2 | 2 | 0 | 0 | 100% |
| Phase 2 | 9 | 5 | 3 | 1 | 63% |
| Phase 3 | 4 | 0 | 3 | 0 | 0% |
| Phase 4 | 3 | 1 | 2 | 0 | 33% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
GABA-T Drug Approval Timeline (2009 - 2024)
The first GABA-T drug was approved in 2009 (Sabril), with the most recent in 2024 (Vigafyde).
The 16-year approval span indicates a sustained interest in GABA-T as a drug target.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 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
- • Sponsors: 14 (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 GABA-T. A trial counts if an approved drug acting on GABA-T 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.