PARP1 Inhibitors
5 drugsAbout PARP1
PARP1 (poly (ADP-ribose) polymerase 1) is an enzyme involved in DNA repair and other cellular processes. It plays a crucial role in repairing damaged DNA, making it a compelling target for therapeutic intervention, particularly in cancer.
Human genetic studies provide strong validation for PARP1 as a therapeutic target in diseases like clonal hematopoiesis (score 0.78) and cutaneous melanoma (score 0.77). Loss-of-function variants are associated with increased disease risk, supporting inhibition-based therapies.
PARP1 is targeted by two FDA-approved small molecule drugs, LYNPARZA (AstraZeneca) and TALZENNA (Pfizer), both used in oncology. LYNPARZA has 4 indications, while TALZENNA has 2, highlighting their clinical utility.
PARP1 Genetic Evidence Strong
PARP1 has strong genetic support with a max score of 0.78 across 10 diseases.
Strong genetic support suggests a higher likelihood of clinical trial success for PARP1-targeting drugs.
Evidence Across Diseases
10 totalGWAS and other genetic studies link PARP1 to 10 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PARP1 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 PARP1 Drugs
The competitive landscape is concentrated, with AstraZeneca and Pfizer holding all approved drugs.
High market concentration suggests significant barriers to entry, requiring differentiated strategies for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TALZENNA | Pfizer | 2018 | 2 |
| AKEEGA | Johnson & Johnson | 2023 | 1 |
PARP1 Drug Modality Landscape
Modalities
Routes of Administration
PARP1 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or PROTACs could provide a competitive advantage in the PARP1 space.
PARP1 Clinical Trials 845 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on PARP1. 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 PARP1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting PARP1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
PARP1 Drug Approval Timeline (2016 - 2023)
The approval timeline spans 5 years, with LYNPARZA approved in 2014 and TALZENNA in 2018.
The relatively short approval span suggests potential for further innovation and market growth in PARP1 inhibition.
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 PARP1. A trial counts if an approved drug acting on PARP1 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.