FDA Grants Accelerated Approval to Olaparib, Companion Diagnostic for Treatment of Advanced Ovarian Cancer

The FDA today granted accelerated approval to olaparib, a poly ADP-ribose polymerase (PARP) inhibitor, for treatment of advanced ovarian cancer in women with defected BRCA genes, along with a companion diagnostic test that marked the agency's first approval of a laboratory developed test (LDT) under a premarket approval application.

The FDA today granted accelerated approval to olaparib, a poly ADP-ribose polymerase (PARP) inhibitor, for treatment of advanced ovarian cancer in women with defected BRCA genes, along with a companion diagnostic test that marked the agency’s first approval of a laboratory developed test (LDT) under a premarket approval application.

Olaparib, marketed by Astra Zeneca as Lynparza, blocks enzymes involved in repairing damaged DNA. The treatment will be for women who have received at least 3 prior lines of chemotherapy.

“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.”

Ovarian cancer forms in the ovary, one of a pair of female reproductive glands where ova, or eggs, are formed. The National Cancer Institute estimates that 21,980 American women will be diagnosed with and 14,270 will die from ovarian cancer in 2014.

Approved with olaparib is the companion diagnostic BRACAnalysis CDx, made by Myriad Genetics. The test is designed to detect mutations in the BRCA genes 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 percent 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 used 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 approval of safe and effective companion diagnostic tests and drugs continue to be important developments in oncology,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “We are very excited that the BRACAnalysis CDx is the FDA’s first approval of an LDT under a premarket approval application and is the first approval of an LDT companion diagnostic. The use of companion diagnostics helps bring to market safe and effective treatments specific to a patient’s needs.”

Olaparib’s efficacy was examined in a study where 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 percent of participants experienced ORR for an average of 7.9 months.

Common side effects of the drug included nausea, fatigue, vomiting, diarrhea, distorted taste (dysgeusia), indigestion (dyspepsia), headache, decreased appetite, common cold-like symptoms (nasopharyngitis), cough, joint paint (arthralgia), musculoskeletal pain, muscle pain (myalgia), back pain, rash (dermatitis) and abdominal pain. Serious side effects included the development of myelodysplastic syndrome, a condition where the bone marrow is unable to produce enough functioning blood cells; acute myeloid leukemia, a bone marrow cancer; and lung inflammation.

According to a statement, today’s approval is Myriad’s first for a companion diagnostic for use with a novel PARP inhibitor. Mark Capone, president of Myriad Genetic Laboratories, said in a statement, “We believe (this) opens a door in personalized medicine and represents a big step forward in tailoring treatment for women with ovarian cancer.”