{"id":"olaparib-oral-product","rwe":[],"tags":[],"phase":"discontinued","safety":{"boxedWarnings":[],"drugInteractions":[],"commonSideEffects":[],"contraindications":[],"specialPopulations":{"Pregnancy":"Data not available","Geriatric use":"Data not available","Paediatric use":"Data not available","Renal impairment":"Data not available","Hepatic impairment":"Data not available"},"seriousAdverseEvents":[]},"status":"discontinued","trials":["NCT03167619","NCT05233982","NCT04780945"],"aliases":["Olaparib tablet"],"patents":[],"pricing":[],"offLabel":[],"timeline":[{"date":"","type":"neutral","milestone":"Olaparib oral product development initiated at Duke University","regulator":"none","description":"Duke University began development of an oral olaparib formulation for PARP inhibition in cancer."},{"date":"","type":"positive","milestone":"Phase 1 trials initiated in BRCA-mutated and HRD-positive tumors","regulator":"none","description":"Multiple Phase 1 studies launched including combination with ASTX727 and single-agent trials in advanced solid tumors."},{"date":"","type":"positive","milestone":"Phase 2 trials expanded to prostate, breast, and ovarian cancers","regulator":"none","description":"Phase 2 studies initiated in advanced prostate adenocarcinoma, BRCA-mutated breast cancer, and ovarian cancer with various combination partners."},{"date":"","type":"positive","milestone":"Phase 3 trial in platinum-resistant ovarian cancer initiated","regulator":"none","description":"Phase 3 study of olaparib plus alpelisib in platinum-resistant/refractory high-grade serous ovarian cancer enrolled 358 patients."},{"date":"","type":"positive","milestone":"Phase 4 trial completed in metastatic castration-resistant prostate cancer","regulator":"none","description":"Phase 4 study assessing efficacy and safety in Chinese patients with mCRPC completed with 43 patients."},{"date":"","type":"positive","milestone":"Pembrolizumab combination trial completed in BRCA-mutated breast cancer","regulator":"none","description":"Phase 2 trial of olaparib plus pembrolizumab in advanced BRCA-mutated or HDR-deficient breast cancer completed with 14 patients."},{"date":"","type":"negative","milestone":"Phase 3 alpelisib combination trial terminated","regulator":"none","description":"Phase 3 study of olaparib plus alpelisib in platinum-resistant ovarian cancer terminated after enrolling 358 patients."},{"date":"","type":"negative","milestone":"Phase 1 NUV-868 combination trial terminated","regulator":"none","description":"Phase 1 trial of NUV-868 in combination with olaparib or enzalutamide terminated after enrolling 82 patients."},{"date":"","type":"negative","milestone":"Phase 1 functional analysis trial terminated","regulator":"none","description":"Phase 2 functional analysis of BRCAness trial terminated after enrolling 27 patients with ovarian neoplasm."},{"date":"","type":"negative","milestone":"Duke University olaparib oral product discontinued","regulator":"none","description":"Duke University discontinued development of olaparib oral product; likely due to competitive landscape dominated by AstraZeneca's Lynparza®."}],"aiSummary":"Olaparib oral product is a PARP (poly-ADP-ribose polymerase) inhibitor developed by Duke University, currently in discontinued status. The drug works by inhibiting PARP enzymes, which are critical for DNA repair in cancer cells, particularly those with BRCA1/2 mutations or homologous recombination deficiency (HRD). While no FDA-approved indications are listed for the Duke formulation, olaparib has extensive clinical trial activity across 50 trials spanning Phase 1–4, with notable studies in BRCA-mutated breast and ovarian cancers, prostate cancer, and combination therapies with immunotherapies and targeted agents. The clinical pipeline demonstrates broad oncology application, though the discontinued status suggests Duke may have deprioritized development in favor of the commercially available AstraZeneca olaparib (Lynparza®). Competitive positioning is challenged by the established market presence of Lynparza and other PARP inhibitors (rucaparib, niraparib), which have secured multiple regulatory approvals and substantial market penetration in HRD-positive and BRCA-mutated malignancies.","brandName":"Olaparib Oral Product","companyId":"duke-university","ecosystem":[],"mechanism":{"target":"PARP-1 and PARP-2 (poly-ADP-ribose polymerase enzymes)","novelty":"me-too","modality":"small molecule","drugClass":"PARP inhibitor (DNA repair inhibitor)","explanation":"Olaparib works by blocking PARP enzymes, which are responsible for repairing single-strand DNA breaks in cells. In normal cells, this repair mechanism is redundant—cells can use homologous recombination (HR) as an alternative pathway. However, cancer cells with BRCA1/2 mutations or other HR deficiencies cannot use this backup pathway. When olaparib blocks PARP, these deficient cancer cells accumulate unrepaired DNA damage, leading to cell death. This creates a synthetic lethal interaction: the drug is selectively toxic to HR-deficient tumors while sparing most normal cells that retain functional HR. The oral formulation allows convenient at-home dosing compared to intravenous alternatives.","oneSentence":"Olaparib inhibits poly-ADP-ribose polymerase (PARP) enzymes to impair DNA repair in cancer cells with BRCA mutations or homologous recombination deficiency.","technicalDetail":"Olaparib is a small-molecule PARP inhibitor that binds to the catalytic domain of PARP-1 and PARP-2, preventing NAD+ binding and blocking poly(ADP-ribosyl)ation. The drug demonstrates selectivity for PARP over other enzymes and achieves oral bioavailability suitable for twice-daily dosing. Pharmacokinetically, olaparib undergoes hepatic metabolism via CYP3A4 and glucuronidation, with a half-life permitting BID administration. The mechanism exploits synthetic lethality in BRCA1/2-mutated and HRD-positive tumors, where single-agent PARP inhibition induces irreparable DNA damage."},"commercial":{"notes":"Duke University product discontinued; commercial olaparib (Lynparza®) marketed by AstraZeneca with peak sales >$1.5B globally","yoyGrowth":"","launchDate":"","marketShare":"","revenueYear":"","annualCostUS":"","currentRevenue":"","percentOfCompany":"","patientPopulation":"","peakSalesEstimate":"","genericCompetition":"no"},"references":[],"biosimilars":[],"companyName":"Duke University","competitors":[{"name":"Olaparib (Lynparza®)","slug":"olaparib-lynparza","company":"AstraZeneca","advantage":"FDA-approved, established market presence, multiple indication approvals in BRCA-mutated and HRD-positive cancers"},{"name":"Rucaparib (Rubraca®)","slug":"rucaparib-rubraca","company":"Clovis Oncology","advantage":"FDA-approved PARP inhibitor for ovarian and prostate cancer; alternative mechanism profile"},{"name":"Niraparib (Zejula®)","slug":"niraparib-zejula","company":"GlaxoSmithKline","advantage":"FDA-approved PARP inhibitor with broad ovarian cancer indications; maintenance therapy approved"},{"name":"Talazoparib (Talquetamab®)","slug":"talazoparib","company":"Pfizer","advantage":"PARP inhibitor in development; potential differentiation in BRCA-mutated breast cancer"},{"name":"Pamiparib (BGB-290)","slug":"pamiparib-bgb-290","company":"BeiGene","advantage":"PARP inhibitor approved in China; expanding global development in HRD-positive tumors"}],"genericName":"Olaparib Oral Product","indications":{"approved":[],"offLabel":[],"pipeline":[{"name":"BRCA1/2-mutated and HRD-positive advanced solid tumors","notes":"Combination study with ASTX727 in BRCA1/2-mutated and HRD-mutated tumors; 18 patients enrolled","phase":"Phase 1","status":"recruiting"},{"name":"Muscle-invasive bladder cancer","notes":"Open-label, randomized, multi-drug biomarker-directed study; 117 patients; AstraZeneca sponsor","phase":"Phase 1","status":"active"},{"name":"Advanced prostate adenocarcinoma with neuroendocrine differentiation","notes":"Combination with cediranib vs. olaparib monotherapy; 90 patients; NCI sponsor","phase":"Phase 2","status":"active"},{"name":"Advanced BRCA-mutated or HDR-deficient breast cancer","notes":"Combination with pembrolizumab; 14 patients; completed trial","phase":"Phase 2","status":"completed"},{"name":"Platinum-resistant/refractory high-grade serous ovarian cancer","notes":"Combination with alpelisib; 358 patients; Novartis sponsor; trial terminated","phase":"Phase 3","status":"terminated"}]},"labelChanges":[],"relatedDrugs":[],"trialDetails":[{"nctId":"NCT06966700","phase":"PHASE3","title":"A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)","status":"RECRUITING","sponsor":"Merck Sharp & Dohme LLC","startDate":"2025-06-30","conditions":"Breast Neoplasms, Triple Negative Breast Neoplasms, HR 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Tumors","enrollment":5000},{"nctId":"NCT04729387","phase":"PHASE3","title":"Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected","status":"TERMINATED","sponsor":"Novartis Pharmaceuticals","startDate":"2021-07-22","conditions":"Ovarian Cancer","enrollment":358},{"nctId":"NCT02502266","phase":"PHASE2, PHASE3","title":"Testing the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2016-05-03","conditions":"Fallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube Serous Adenocarcinoma","enrollment":582},{"nctId":"NCT04780945","phase":"PHASE2","title":"Functional Analysis of BRCAness","status":"TERMINATED","sponsor":"Leiden University Medical 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w/ Muscle Invasive Bladder Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"AstraZeneca","startDate":"2016-12-28","conditions":"Muscle Invasive Bladder Cancer","enrollment":117},{"nctId":"NCT06545942","phase":"PHASE1","title":"Study of Orally Administered MOMA-313 in Participants With Advanced or Metastatic Solid Tumors","status":"RECRUITING","sponsor":"MOMA Therapeutics","startDate":"2024-08-13","conditions":"Advanced Solid Tumor, Metastatic Solid Tumor, Prostate Cancer","enrollment":220},{"nctId":"NCT05457257","phase":"PHASE4","title":"Clinical Study to Assess the Efficacy and Safety of Olaparib in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations","status":"COMPLETED","sponsor":"AstraZeneca","startDate":"2022-07-29","conditions":"Metastatic Castration-resistant Prostate Cancer","enrollment":43}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"icon":"💊","route":"oral","frequency":"Data not available","formulation":"Data not available"},"formularyStatus":[],"apiManufacturers":[],"developmentCodes":[],"ownershipHistory":[{"notes":"Duke University developed olaparib oral product; project discontinued","period":"Development–discontinued","companyName":"Duke University","relationship":"Originator"}],"therapeuticAreas":["Oncology"],"trialPhaseCounts":{"PHASE1":9,"PHASE2":24,"PHASE3":5,"PHASE4":1,"EARLY_PHASE1":2,"PHASE1, PHASE2":7,"PHASE2, PHASE3":2},"biosimilarFilings":[],"firstApprovalDate":"","companionDiagnostics":[],"firstApprovalCountry":null,"genericManufacturerList":[],"modality":"Small molecule","enrichmentLevel":3,"visitCount":1,"trialStats":{"total":4,"withResults":1},"verificationStatus":"partial","dataCompleteness":{"mechanism":true,"indications":false,"safety":false,"trials":true,"score":2}}