PARP-2 Inhibitors
5 drugsAbout PARP-2
PARP-2, or Poly (ADP-ribose) polymerase 2, is involved in DNA repair mechanisms. It has garnered attention as a potential therapeutic target, particularly in oncology.
Genetic evidence weakly supports PARP-2's role in disease, with associations to insomnia (score 0.04). However, strong eQTL/pQTL signals (max H4: 1.00) suggest potential regulatory roles.
Three FDA-approved small molecule drugs target PARP-2: ZEJULA, AKEEGA, and RUBRACA. These drugs, developed by GSK, Johnson & Johnson, and PHARMAAND, are all used in oncology.
PARP-2 Genetic Evidence
Genetic evidence for PARP-2 is weak (max score 0.04), but colocalization data shows strong eQTL/pQTL signals.
Low genetic support suggests focusing on indications with strong mechanistic rationale or biomarker enrichment.
Evidence Across Diseases
1 totalGWAS and other genetic studies link PARP2 to 1 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PARP2 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 PARP-2 Drugs
Three companies, GSK, Johnson & Johnson, and PHARMAAND, have approved PARP-2 drugs.
Limited competition suggests opportunities for new entrants, but also highlights potential market challenges.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TALZENNA | Pfizer | 2018 | 2 |
| AKEEGA | Johnson & Johnson | 2023 | 1 |
PARP-2 Drug Modality Landscape
Modalities
Routes of Administration
PARP-2 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like PROTACs or degraders could offer differentiation and IP advantages.
PARP-2 Clinical Trials 845 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on PARP-2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 297 | 128 | 61 | 108 | 68% |
| Phase 2 | 437 | 156 | 87 | 193 | 64% |
| Phase 3 | 97 | 34 | 5 | 58 | 87% |
| Phase 4 | 14 | 6 | 0 | 8 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
6 Phase 3 trials testing approved PARP-2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting PARP-2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
PARP-2 Drug Approval Timeline (2016 - 2023)
The first PARP-2 drug was approved in 2016, with the most recent in 2023.
Recent approval suggests continued interest, but increasing saturation warrants careful market positioning.
Pro Intelligence Preview
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: 314 (83 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 PARP-2. A trial counts if an approved drug acting on PARP-2 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.