AstraZeneca’s (AZ) new ovarian cancer candidate olaparib has been accepted for review by the European Medicines Agency, setting up a possible approval next year.
Olaparib is among the first drugs in the new PARP (poly ADP-ribose polymerase) inhibitor class to come through development and is being investigated for maintenance treatment of patients with BRCA mutated platinum-sensitive relapsed serous ovarian cancer.
PARP inhibitors are designed to treat cancer by blocking the repair of DNA in tumour cells, although some of the early drug candidates – notably Sanofi’s iniparib – ran into hurdles and had to be withdrawn from development.
AZ also reported disappointing phase II trial results with olaparib in 2011 in a more generalised group of ovarian cancer patients and suggested it would shelve the project. However, a re-analysis of the data in BRCA-positive patients – coupled with a reformulation of the drug – convinced the pharma company to think again and keep it going.
The EMA filing is based on the results of a phase II trial – called Study 19 – that compared maintenance treatment with olaparib to placebo in platinum-sensitive relapsed serous ovarian cancer patients.
The patients had all received previous treatment with at least two platinum regimens and were in a maintained partial or complete response. Olaparib was found to be superior to placebo on the primary outcome of progression-free survival (PFS), as well as a number of additional efficacy measures.
A new class of therapeutic agents are desperately needed in ovarian cancer because platinum-based chemotherapy can only be given for a limited number of cycles before the side effects become intolerable.
Olaparib and other PARP inhibitors coming through development are oral agents with much better tolerability so they can be given for much longer than conventional chemotherapy.
Approval would likely make olaparib the first PARP inhibitor to reach the market, and the company is busily conducting phase III trials in patients with BRCA1/2 mutations to back up any conditional approval on the basis of the phase II dataset.
Following most closely is Tesaro’s niraparib, a Merck & Co-developed compound which has reached phase III testing but has yet to be submitted for marketing. Meanwhile, Clovis Oncology’s rucaparib (formerly developed by Pfizer), AbbVie’s veliparib and BioMarin’s BMN 673 are in early- to mid-stage testing.