The Food and Drug Administration has granted accelerated approval to olaparib (Lynparza, made by AstraZeneca) to treat women with advanced ovarian cancer associated with defective BRCA genes, as detected by an FDA-approved test-i.e., in this case, Myriad's BRACAnalysis CDx, which was approved at the same time.
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.
"The approval constitutes the first of a new class of drugs for treating ovarian cancer," said Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products. "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 approval was accompanied by approval of the companion BRACAnalysis CDx diagnostic to detect the presence of mutations in 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 an estimated 10 to 15 percent of all ovarian cancer is thought to be associated with hereditary BRCA mutations.
As explained in an FDA news release, the agency evaluated BRACAnalysis CDx's safety and efficacy under the premarket approval pathway used for high-risk medical devices. Until now, the manufacturer, a clinical laboratory, had been marketing the test-although not specifically as a companion diagnostic-without FDA approval as a laboratory-developed test (LDT)-i.e., a test designed, manufactured, and used in a single laboratory.
"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 FDA's Office of In Vitro Diagnostics 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."
Common side effects of Lynparza included nausea, fatigue, vomiting, diarrhea, distorted taste (dysgeusia), indigestion, headache, decreased appetite, common cold-like symptoms, 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 average volume of red blood cells, decreased red blood cell count, decreased white blood cell count, and decreased platelet levels.
In June, Lynparza was reviewed by the FDA's Oncologic Drugs Advisory Committee for potential use as maintenance therapy, but the vote was 11 to 2 that the data did not support accelerated approval for this use. After the meeting, the company submitted additional information supporting Lynparza's use for a different use: in patients with mutated BRCA genes (gBRCAm)-associated ovarian cancer who have received three or more chemotherapy treatments.