SV2A Inhibitors
6 drugsAbout SV2A
Synaptic Vesicle Glycoprotein 2A (SV2A) is a transmembrane protein in the brain that regulates neurotransmitter release. Its role in neurotransmitter release makes it a compelling target for therapeutic intervention.
Human genetic studies provide strong validation for SV2A as a therapeutic target (max score 0.84). Genetic variants are linked to skeletal abnormalities (score 0.84), developmental and epileptic encephalopathy (score 0.76), and type 2 diabetes (score 0.58), suggesting activation may be beneficial.
SV2A is targeted by 6 FDA-approved small molecule drugs, including LEVETIRACETAM (KEPPRA) and BRIVIACT. These drugs are used for CNS disorders and other therapeutic areas.
SV2A Genetic Evidence Strong
SV2A has strong genetic support with a max score of 0.84 across 13 diseases.
Strong genetic support suggests SV2A-targeting drugs have a higher probability of clinical success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
13 totalGWAS and other genetic studies link SV2A to 13 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for SV2A 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 SV2A Drugs
Four companies have approved drugs targeting SV2A, including ZYDUS PHARMS USA INC and UCB INC.
The competitive landscape indicates moderate market concentration, suggesting potential entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| KEPPRA | UCB INC | 1999 | 3 |
| BRIVARACETAM | Aurobindo Pharma | 2022 | 1 |
| KEPPRA XR | UCB INC | 2008 | 1 |
SV2A Drug Modality Landscape
Modalities
Routes of Administration
SV2A is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape suggests an opportunity to develop non-small molecule drugs targeting SV2A.
SV2A Clinical Trials 183 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on SV2A. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 34 | 27 | 3 | 4 | 90% |
| Phase 2 | 53 | 28 | 13 | 12 | 68% |
| Phase 3 | 54 | 31 | 8 | 15 | 79% |
| Phase 4 | 42 | 26 | 8 | 7 | 76% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved SV2A drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting SV2A. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
SV2A Drug Approval Timeline (1999 - 2022)
The first SV2A-targeting drug was approved in 1999 (KEPPRA), with the most recent in 2022 (BRIVARACETAM).
The approval timeline indicates continued interest in SV2A 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 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: 127 (23 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 SV2A. A trial counts if an approved drug acting on SV2A 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.