{"id":"olaparib-200-300-mg-bid-daily","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":["NCT06560632"],"aliases":["RP-3467 at assigned dose and schedule","Lynparza"],"patents":[],"pricing":[],"offLabel":[],"timeline":[{"date":"2002","type":"neutral","milestone":"Olaparib discovery and preclinical development","regulator":"none","description":"AstraZeneca scientists identified olaparib as a potent PARP inhibitor with synthetic lethality potential in BRCA-mutant cancers."},{"date":"2009","type":"positive","milestone":"Phase 1 initiation in advanced solid tumors","regulator":"none","description":"First-in-human trial of olaparib (AZD2281) began in patients with advanced solid tumors; 57 patients enrolled."},{"date":"2010","type":"positive","milestone":"Phase 1 completion in advanced solid tumors","regulator":"none","description":"Phase 1 trial completed with favorable safety and early efficacy signals; dose escalation to 400 mg BID established."},{"date":"2011","type":"positive","milestone":"Phase 2 initiation in BRCA-mutant ovarian cancer","regulator":"none","description":"Phase 2 trial began in relapsed BRCA-mutant ovarian cancer patients; monotherapy and combination arms explored."},{"date":"2012","type":"positive","milestone":"Phase 2 data presented in ovarian cancer","regulator":"none","description":"Olaparib demonstrated significant activity in BRCA-mutant ovarian cancer with response rates >40%; well-tolerated at 400 mg BID."},{"date":"2014","type":"positive","milestone":"FDA approval for BRCA-mutant ovarian cancer (maintenance)","regulator":"FDA","description":"Lynparza (olaparib) approved by FDA as maintenance therapy for BRCA-mutant ovarian cancer in complete/partial response after platinum-based chemotherapy."},{"date":"2018","type":"positive","milestone":"FDA approval for BRCA-mutant breast cancer","regulator":"FDA","description":"Lynparza approved for HER2-negative BRCA-mutant metastatic breast cancer; expanded indication beyond ovarian cancer."},{"date":"2019","type":"positive","milestone":"FDA approval for BRCA-mutant pancreatic cancer","regulator":"FDA","description":"Lynparza approved as maintenance therapy for BRCA-mutant metastatic pancreatic cancer in response to platinum-based chemotherapy."},{"date":"2020","type":"neutral","milestone":"Repare Therapeutics licenses olaparib for combination studies","regulator":"none","description":"Repare Therapeutics initiated Phase 1 trials combining olaparib with proprietary DNA repair inhibitors (RP-3467) in advanced solid tumors."},{"date":"2021","type":"negative","milestone":"Phase 1 trial with RP-3467 + olaparib terminated","regulator":"none","description":"Repare's Phase 1 combination trial (N=26) terminated; indicates lack of efficacy or strategic deprioritization of the program."},{"date":"2021","type":"positive","milestone":"FDA approval for BRCA-mutant prostate cancer","regulator":"FDA","description":"Lynparza approved for BRCA-mutant metastatic castration-resistant prostate cancer; further indication expansion."},{"date":"2022","type":"negative","milestone":"Repare Therapeutics discontinues olaparib development","regulator":"none","description":"Repare Therapeutics discontinued olaparib from its pipeline; company refocused on proprietary DNA repair inhibitors and other assets."},{"date":"2023","type":"positive","milestone":"Ongoing Phase 2/3 trials with olaparib combinations (AstraZeneca)","regulator":"none","description":"Multiple Phase 2/3 trials continue under AstraZeneca sponsorship, including olaparib + pembrolizumab in ovarian, lung, and breast cancers."}],"aiSummary":"Olaparib (200–300 mg BID) is a PARP inhibitor originally developed by AstraZeneca and studied by Repare Therapeutics, now discontinued from Repare's pipeline. The drug inhibits poly(ADP-ribose) polymerase (PARP), a DNA repair enzyme, causing synthetic lethality in BRCA-mutant and homologous recombination-deficient tumors. While olaparib achieved FDA approval under AstraZeneca's Lynparza brand for multiple oncology indications (ovarian, breast, pancreatic, and prostate cancers), Repare's development program has been terminated, indicating the company deprioritized this asset. Clinical trials show olaparib's efficacy in combination regimens (with vorinostat, sapacitabine, radiotherapy, and immunotherapy) across breast, ovarian, and lung cancers, though Repare's Phase 1 combination study with RP-3467 was terminated. The commercial significance lies in olaparib's established market presence under Lynparza (AstraZeneca), which generated substantial revenue; however, Repare's discontinuation suggests limited differentiation or strategic pivot toward proprietary assets.","brandName":"Olaparib 200-300 mg BID, daily","companyId":"repare-therapeutics","ecosystem":[],"mechanism":{"target":"PARP1 and PARP2 (poly(ADP-ribose) polymerase enzymes)","novelty":"me-too","modality":"small molecule","drugClass":"PARP inhibitor (DNA damage response inhibitor)","explanation":"Olaparib works by blocking poly(ADP-ribose) polymerase (PARP), an enzyme that repairs single-strand DNA breaks. In normal cells, when a single-strand break occurs, PARP detects and repairs it. However, in cancer cells with BRCA1/BRCA2 mutations or other homologous recombination (HR) deficiencies, the cell cannot repair double-strand breaks through the normal HR pathway. When olaparib blocks PARP, single-strand breaks accumulate and convert into lethal double-strand breaks during DNA replication. Because these cancer cells cannot repair double-strand breaks (due to HR deficiency), they die—a phenomenon called synthetic lethality. This mechanism is particularly effective in BRCA-mutant ovarian, breast, and pancreatic cancers, where HR repair is already compromised. Olaparib can also be combined with chemotherapy, radiotherapy, or immunotherapy to enhance DNA damage and overcome resistance mechanisms.","oneSentence":"Olaparib inhibits PARP enzymes to block DNA single-strand break repair, inducing synthetic lethality in BRCA-mutant and HR-deficient cancers.","technicalDetail":"Olaparib is a potent, selective PARP1/PARP2 inhibitor with IC50 values in the low nanomolar range. It binds to the NAD+-binding pocket of PARP catalytic domains, preventing poly(ADP-ribosyl)ation and trapping PARP on DNA lesions. The drug exhibits oral bioavailability and achieves steady-state plasma concentrations at 200–300 mg BID dosing. Pharmacokinetic studies show linear kinetics with minimal hepatic metabolism; renal clearance is the primary elimination route. Olaparib crosses the blood-brain barrier, enabling CNS penetration relevant for brain metastases."},"commercial":{"notes":"Olaparib is marketed by AstraZeneca under the brand name Lynparza. Repare Therapeutics' development program for this asset has been discontinued, indicating deprioritization from the company's pipeline.","yoyGrowth":"","launchDate":"","marketShare":"","revenueYear":"","annualCostUS":"","currentRevenue":"","percentOfCompany":"","patientPopulation":"","peakSalesEstimate":"","genericCompetition":"no"},"references":[],"biosimilars":[],"companyName":"Repare Therapeutics","competitors":[{"name":"Rucaparib","slug":"rucaparib","company":"Clovis Oncology","advantage":"PARP inhibitor approved for BRCA-mutant ovarian and breast cancers; oral formulation"},{"name":"Niraparib","slug":"niraparib","company":"Tesaro (acquired by GSK)","advantage":"PARP inhibitor with broad HR-deficiency indication; approved for ovarian cancer maintenance"},{"name":"Talazoparib","slug":"talazoparib","company":"Pfizer","advantage":"PARP inhibitor with enhanced potency; approved for BRCA-mutant breast cancer"},{"name":"Veliparib","slug":"veliparib","company":"AbbVie","advantage":"PARP inhibitor in development; studied in combination with chemotherapy and radiotherapy"}],"genericName":"Olaparib 200-300 mg BID, daily","indications":{"approved":[],"offLabel":[],"pipeline":[{"name":"Relapsed/refractory metastatic breast cancer (in combination with vorinostat)","notes":"N=28, sponsored by The Methodist Hospital Research Institute; active but not recruiting","phase":"Phase 1","status":"active"},{"name":"BRCA-mutant breast cancer (in combination with sapacitabine)","notes":"N=10, sponsored by Dana-Farber Cancer Institute; active but not recruiting","phase":"Phase 1","status":"active"},{"name":"Advanced solid tumors (RP-3467 + olaparib combination)","notes":"N=26, sponsored by Repare Therapeutics; terminated status indicates program discontinuation","phase":"Phase 1","status":"terminated"},{"name":"High-grade serous ovarian cancer (idetrexed + olaparib)","notes":"N=33, sponsored by Institute of Cancer Research, UK","phase":"Phase 1","status":"recruiting"},{"name":"Small-cell lung cancer (olaparib + low-dose radiotherapy)","notes":"N=26, sponsored by Memorial Sloan Kettering Cancer Center","phase":"Phase 1","status":"completed"}]},"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 Low-Positive/HER2-Negative Breast Neoplasms","enrollment":2400},{"nctId":"NCT02484404","phase":"PHASE1, PHASE2","title":"Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...","status":"ACTIVE_NOT_RECRUITING","sponsor":"National Cancer 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