GABA-B Inhibitors
5 drugsAbout GABA-B
Gamma-aminobutyric acid type B receptors (GABA-B) are neuronal targets in the central nervous system activated by GABA. They play a crucial role in inhibitory neurotransmission, modulating neuronal excitability and synaptic transmission.
Human genetic studies provide strong validation for GABBR1 as a therapeutic target, with variants linked to neurodevelopmental disorder with language delay (score 0.77). Additional associations include global developmental delay and intellectual disability (score 0.62).
GABA-B is targeted by 3 FDA-approved small molecule drugs including XYWAV, XYREM and SODIUM OXYBATE. These drugs are approved for 3 therapeutic areas and marketed by companies including ASCENT PHARMS INC, JAZZ, and JAZZ PHARMS.
GABA-B Genetic Evidence Strong
GABBR1 has strong genetic support with a maximum score of 0.77 linking it to neurodevelopmental disorders.
Strong genetic support suggests a higher likelihood of success in clinical trials targeting GABBR1.
Evidence Across Diseases
8 totalGWAS and other genetic studies link GABBR1 to 8 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 GABA-B Drugs
The GABA-B drug market is concentrated among 3 companies, including ASCENT PHARMS INC and JAZZ PHARMS.
The limited number of players indicates relatively low competitive intensity, potentially easing market entry.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| SODIUM OXYBATE | AMNEAL | 2017 | 2 |
| GABLOFEN | PIRAMAL CRITICAL | 2010 | 1 |
GABA-B Drug Modality Landscape
Modalities
Routes of Administration
GABA-B is amenable to small molecule drugs, with oral options available for convenient dosing.
The exclusive use of small molecules suggests a whitespace opportunity for novel modalities like antibodies or peptides.
GABA-B Clinical Trials 87 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on GABA-B. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 11 | 9 | 1 | 1 | 90% |
| Phase 2 | 35 | 21 | 7 | 7 | 75% |
| Phase 3 | 14 | 11 | 1 | 2 | 92% |
| Phase 4 | 27 | 17 | 6 | 3 | 74% |
Top Sponsors
By Modality
GABA-B Drug Approval Timeline (2002 - 2022)
The first GABA-B targeting drug was approved in 2002 (XYREM), with the most recent approval in 2020 (XYWAV).
The approval timeline indicates continued interest in GABA-B as a drug target, but may be approaching saturation.
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Deep insights for drug target analysis
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
- • Sponsors: 70 (9 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-B. A trial counts if an approved drug acting on GABA-B 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.