An overview of olaparib approved by FDA


Olaparib, also known as AZD-2281 or KU-59436, is a small molecule inhibitor of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) with potential chemosensitizing, radiosensitizing, and antineoplastic activities. Olaparib selectively binds to and inhibits PARP, inhibiting PARP-mediated repair of single strand DNA breaks. PARP inhibition may enhance the cytotoxicity of DNA-damaging agents and may reverse tumor cell chemoresistance and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins and can be activated by single-stranded DNA breaks.

Three PARP inhibitors are currently approved for marketing worldwide. In addition to Lynparza, they include Rubraca (rucaparib) from Clovis Oncology and Zejula (niraparib) from Tesaro. But they are currently limited to indications for ovarian cancer.

We sort out an overview of olaparib approved by FDA.

On December 19, 2014, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Lynparza (olaparib), a new drug treatment for women with advanced ovarian cancer associated with defective BRCA genes, as detected by an FDA-approved test.

On August 17, 2017, AstraZeneca and Merck & Co., Inc. announced that the FDA has granted approval for the PARP inhibitor, Lynparza (olaparib), as follows:

  1. New use of Lynparza tablets as a maintenance treatment of adult patients with recurrent, epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy, regardless of BRCA status;
  2. New use of Lynparza tablets (2 tablets twice daily) as opposed to capsules (8 capsules twice daily);
  3. Lynparza tablets also now indicated for the use in adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCA) advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy; patients for this indication are selected for therapy based on an FDA-approved companion diagnostic.

On January 12, 2018, The FDA expanded the approved use of Lynparza (olaparib) to include the treatment of patients with certain types of breast cancer that have spread (metastasized) and whose tumors have a specific inherited (germline) genetic mutation, making it the first drug in its class (PARP inhibitor) approved to treat breast cancer, and it is the first time any drug has been approved to treat certain patients with metastatic breast cancer who have a “BRCA” gene mutation.

The FDA approved Lynparza with a genetic test called BRACAnalysis CDx, 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 percent of all ovarian cancer is associated with these hereditary BRCA mutations.

Common side effects of Lynparza include low levels of red blood cells (anemia), low levels of certain white blood cells (neutropenia, leukopenia), nausea, fatigue, vomiting, common cold (nasopharyngitis), respiratory tract infection, influenza, diarrhea, joint pain (arthralgia/myalgia), unusual taste sensation (dysgeusia), headache, indigestion (dyspepsia), decreased appetite, constipation and inflammation and sores in the mouth (stomatitis).

 

Severe side effects of Lynparza include development of certain blood or bone marrow cancers (myelodysplastic syndrome/acute myeloid leukemia) and inflammation in the lungs (pneumonitis). Lynparza can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. Women taking Lynparza should not breastfeed as it could cause harm to a newborn baby.