But a US regulatory decision is still pending for AstraZeneca's olaparib.

The lowdown: In 2011 and 2012, a series of clinical trial failures threatened poly (ADP-ribose) polymerase (PARP) inhibitors — which modulate the repair of DNA damage — with extinction. Not only did Sanofi's iniparib fail in triple-negative breast cancer, but AstraZeneca's olaparib also disappointed in ovarian cancer. Subsequent studies showed that iniparib is not a functional PARP inhibitor and shed new light on patient selection, fuelling a come-back (Nature Rev. Drug Discov. 12, 725–727; 2013). Olaparib has now secured a full turnaround, receiving a vote of confidence from the European Medicines Agency (EMA) for its use as a monotherapy for the maintenance treatment of women with relapsed BRCA-positive ovarian cancer.

The EMA based their decision on a Phase II trial in 265 women with platinum-sensitive relapsed serous ovarian cancer. The median progression-free survival was 11.2 months with olaparib, versus 4.3 months on placebo (Lancet Oncol. 15, 852–861; 2014). At an interim analysis, overall survival did not differ between treatment groups. The most common adverse events associated with treatment were nausea, vomiting, fatigue and anaemia.

The US Food and Drug Administration was initially set to rule on the drug in October, but has postponed the decision date, probably until January 2015. The delay followed an independent advisory committee meeting in which panellists voted 11 to 2 against accelerated approval of the drug. Panellists debated the side-effect profile of the drug, the use of progression-free survival versus overall survival data, and the ethics of approving the drug while a Phase III confirmatory trial was still enrolling patients.

Olaparib is also in Phase III trials for breast cancer and in Phase II trials for non-small-cell lung cancer, prostate cancer and colorectal cancer.

Four other PARP inhibitor candidates are in hot pursuit. Merck and Tesaro's niraparib, Clovis' rucaparib, BioMarin's talazoparib and AbbVie's veliparib are all in Phase III trials for various oncology indications.