Development of PARP inhibitors for ovarian and breast cancer is equally extensive

16th February 2017 (Last Updated February 16th, 2017 05:15)

A large number of clinical trials evaluating inhibitors of the enzyme poly ADP ribose polymerase (PARP) in breast and ovarian cancers are either ongoing or completed.

A large number of clinical trials evaluating inhibitors of the enzyme poly ADP ribose polymerase (PARP) in breast and ovarian cancers are either ongoing or completed. Despite a similar number of Phase I to III trials for both diseases, with 97 and 86 clinical trials in breast and ovarian cancer, respectively, PARP inhibitors have launched and become practice-changing in ovarian cancer, while development has had setbacks in breast cancer. While developers of PARP inhibitors for the ovarian cancer market are experiencing a rapid return on their R&D investment, those targeting the breast cancer market are awaiting clinical trial success.

PARP inhibitors are targeted therapies that can induce apoptotic processes by altering the DNA repair pathway. These drugs are particularly potent where the cellular DNA repair machinery is already compromised, as in patients with BRCA gene mutations. Gaining ground in the ovarian cancer market, PARP inhibitors such as AstraZeneca’s Lynparza (olaparib), Clovis Oncology’s Rubraca (rucaparib), and the newcomer Tesaro’s niraparib are poised to become standard of care in a significant proportion of patients with recurrent ovarian cancer. In the coming years, GlobalData analysts foresee PARP inhibitors to show additional benefit in ovarian cancer patients, who will use these agents at earlier lines of therapy, even in patients without genetic mutations associated with DNA repair.

Lagging far behind, PARP inhibitors in breast cancer have been rather disappointing. This class of drug already stumbled in 2009, when iniparib, developed by Sanofi Aventis, failed to show efficacy in metastatic breast cancer. Four additional PARP inhibitors (AstraZeneca’s Lynparza, AbbVie’s veliparib, Tesaro’s niraparib, Pfizer’s talazoparib), carrying higher potency, are currently being evaluated in Phase III trials exclusively in BRCA-mutation patients. New Phase II trial data with veliparib combined with chemotherapy agents in BRCA-mutated patients with metastatic disease were presented at the 2016 San Antonio Breast Cancer Symposium; however, the results were disappointing as veliparib failed to meet the primary endpoint of the study, based on an improvement in progression-free survival.

Despite these setbacks, GlobalData anticipates that the variety of PARP inhibitors, with varying potency and combination strategies, will show benefit in breast cancer and generate sales of $1.3 billion by 2023; however, the clinical benefit of PARP inhibitors is in the limelight solely for ovarian cancer patients.