Poly (ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that are used for multiple indications, most commonly, cancer. PARP aids in cellular growth, regulation and repair of cells.The PARP inhibitor stops the cancer cells being repaired which causes the cells to die thus reducing the tumor growth. Numerous cancer forms are more dependent on PARP than regular cells, making it an attractive target for cancer therapy. Currently they are used to treat ovarian cancer, fallopian tube cancer and peritoneal cancer. These inhibitors are considered as a potential treatment for acute life-threatening diseases, such as stroke and myocardial infarction, along with neurodegenerative diseases. Currently this class of drug is becoming popular which can be deduced from the increased research as seen in the below clinical trial data from past few years.
2017 (Till Sep)
Early Phase 1
There have been around 173 studies on PARP inhibitors with 55 completed studies and 3 studies with results. Olaparib, Niraparib and Rucaparib are the commercially available PARP inhibitors.
This is commercially available as Lynparza, produced by AstraZeneca, Inc., (earlier, KuDOS Pharmaceuticals). It is used to treat ovarian cancer, fallopian tube cancer, or peritoneal cancer. It is a monotherapy used in patients with deleterious or suspected deleterious germline BRCA mutated advanced cancer who have been treated with three or more prior lines of chemotherapy. Olaparib also accounts for the highest number of clinical trials; with single drug or in combination with other molecules.
Combinations (completed studies) : Olaparib+
Cervical Cancer, Ovarian Cancer, Breast Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer, Endometrial Cancer
Non Small Cell Lung Cancer
Irinotecan + Cisplatin + Carboplatin
Advanced Solid Tumours
Carboplatin + Anthracycline + Cyclophosphamide
Malignant Solid Tumors
Cisplatin + Gemcitabine
This is the second most researched PARP inhibitor. It is sold under brand name Zejula, marketed by Tesaro, Inc. (earlier developed by Merck). It is used as a maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. It is generally prescribed post chemotherapy in combination with cisplatin, oxaliplatin, carboplatin, or similar, if the patient responded to the mentioned drugs. It generated revenues of $218 million in 2016 as compared to $94 million in 2015.
Combinations (completed studies) : Nirparib+
Recurrence of Solid Tumor Glioblastoma MultiformeMelanoma
It is commercialized as Rubraca, and is marketed by Clovis Oncology (earlier, Pfizer Inc.). It is the third marketed PARP inhibitor used to treat advanced ovarian cancer. It is a monotherapy for treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with 2 or more chemotherapies.
Combinations (completed studies) : Rucaparib+
Advanced Solid Tumors
Sources: Company websites, press releases, annual reports, SEC filings, drugs.com and clinicaltrial.gov.PARP Inhibitors 2017 last edit: 2017-10-30T19:26:44+00:00 da