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FDA Approves Lynparza for Advanced Ovarian Cancer

Drug targets women with defective BRCA genes found by new test

The FDA has granted accelerated approval to olaparib (Lynparza, AstraZeneca Pharmaceuticals), a new medication for women with advanced ovarian cancer associated with defective BRCA genes as detected by an FDA-approved test.

The National Cancer Institute estimates that 21,980 American women will be diagnosed with and 14,270 will die from ovarian cancer in 2014.

Lynparza is a poly ADP-ribose polymerase (PARP) inhibitor that blocks enzymes involved in repairing damaged DNA. It is intended for women with heavily pretreated ovarian cancer that is associated with defective BRCA genes.

“Today’s approval constitutes the first of a new class of drugs for treating ovarian cancer,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “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.”

The FDA approved Lynparza with a genetic test called BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.), a companion diagnostic that will detect the presence of mutations in the BRCA genes (gBRCAm) in blood samples from patients with ovarian cancer. The BRCA genes are involved with repairing damaged DNA and normally work to suppress tumor growth. Women with mutations resulting in defective BRCA genes are more likely to get ovarian cancer, and it is estimated that 10% to 15% of all ovarian cancer is associated with these hereditary BRCA mutations.

The FDA evaluated the BRACAnalysis CDx’s safety and efficacy under the agency’s premarket approval pathway for high-risk medical devices. Until now, the manufacturer, a clinical laboratory, had been marketing this test, although not specifically for use as a companion diagnostic, without FDA approval as a laboratory developed test (LDT), which is a test that is designed, manufactured and used in a single laboratory. The new test is approved as a companion diagnostic, specifically to identify patients with advanced ovarian cancer who may be candidates for treatment with Lynparza.

The FDA’s approval of the BRACAnalysis CDx is based on data from the clinical study used to support approval of Lynparza. Blood samples from clinical trial participants were tested to validate the test’s use for detecting BRCA mutations in this population.

Lynparza’s efficacy was examined in a study in which 137 participants with gBRCAm-associated ovarian cancer received the drug. The study was designed to measure objective response rate (ORR), or the percentage of participants who experienced partial shrinkage or complete disappearance of the tumor. Results showed 34% of participants experienced ORR for an average of 7.9 months.

Common side effects of Lynparza included nausea, fatigue, vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis, cough, arthralgia, musculoskeletal pain, myalgia, back pain, dermatitis, and abdominal pain. Serious side effects included the development of myelodysplastic syndrome, acute myeloid leukemia, and lung inflammation.

The most common laboratory abnormalities were increased creatinine, increased mean corpuscular volume elevation, decreased hemoglobin, decreased lymphocytes and neutrophils, and decreased platelet levels.

In June, Lynparza was reviewed by the FDA’s Oncologic Drugs Advisory Committee for potential use as maintenance therapy. The committee advised the agency in a vote of 11 to 2 that the data did not support Lynparza’s accelerated approval for this use. After the meeting, the company submitted additional information supporting Lynparza for a different use: in patients with gBRCAm-associated ovarian cancer who have received three or more chemotherapy treatments.

The FDA is approving Lynparza under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. Lynparza’s application was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that are intended to treat a serious disease or condition and, if approved, would offer significant improvement compared to marketed products.

BRACAnalysis CDx’s application was reviewed under the FDA’s priority review program for devices, which provides for priority review of devices that meet certain criteria, including that the devices are intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition and, if approved, would offer significant, clinically meaningful advantages compared to marketed products.

Source: FDA; December 19, 2014.

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