乌鸦传媒

WASHINGTON -- The FDA today approved olaparib (Lynparza) for advanced, BRCA-mutated ovarian cancer, the first approval of a drug in the PARP (poly ADP-ribose polymerase) inhibitor class.

In granting accelerated approval of olaparib, the FDA broke ranks with an advisory committee that recommended against it. At a June meeting, members of the Oncologic Drugs Advisory Committee (ODAC) cited concerns about basing the approval on a subgroup analysis of a clinical trial and about an excess of hematologic malignancies in patients treated with olaparib.

The FDA is not bound by advisory committee recommendations, and apparently the agency decided the potential benefits outweighed the concerns. The subgroup analysis of 136 patients with BRCA-mutated ovarian cancer showed a 7-month improvement in progression-free survival among patients treated with olaparib but no improvement in overall survival.

"Today's approval constitutes the first of a new class of drugs for treating ovarian cancer," , director of the FDA Office of Hematology and Oncology Products, said in a statement. "Lynparza is approved for patients with specific abnormalities in the BRCA gene and is an example of how a greater understanding of the underlying mechanisms of disease can lead to targeted, more personalized treatment."

However, the favorable FDA action came with a few strings attached. The approval is contingent on a demonstration of positive results with olaparib in two ongoing phase III clinical trials limited to patients with BRCA-mutated ovarian cancer. One trial is evaluating , and is comparing the PARP inhibitor against standard treatment; both have progression-free survival as the primary endpoint. Results of the maintenance trial are expected in 2015.

The FDA also approved Myriad Genetics' BRACAnalysis CDx test to determine patients' BRCA status as a companion diagnostic, for determining whether an individual patient is a candidate for olaparib.

The test "is the FDA's first approval of an LDT [lab-developed test] under a premarket approval application and is the first approval of an LDT companion diagnostic," , director of the Office of In Vitro Diagnostics and Radiological Health, said in the same FDA statement. "The use of companion diagnostics helps bring to market safe and effective treatments specific to a patient's needs."

The FDA action coincided with an announcement that the European Medicines Agency (EMA) has approved olaparib for advanced, BRCA-mutated ovarian cancer. In contrast to the ODAC recommendation, an EMA advisory committee recommended approval of the drug at an October meeting.

PARP inhibitors work by preventing cancer cells from exploiting a BRCA-conferred deficiency in homologous recombination DNA repair. By restoring normal repair mechanisms, PARP inhibitors allow cells to recover from damage caused by the cancer and by chemotherapy used to treat the cancer.

Olaparib is marketed by AstraZeneca.

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