Article Content

The FDA has granted accelerated approval to rucaparib to treat women with a certain type of ovarian cancer. Rucaparib is approved for women with advanced ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a specific gene mutation (deleterious BRCA) as identified by an FDA-approved companion diagnostic test.

FDA; ovarian cancer.... - Click to enlarge in new windowFDA; ovarian cancer. FDA; ovarian cancer

"Today's approval is another example of the trend we are seeing in developing targeted agents to treat cancers caused by specific mutations in a patient's genes," said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and Acting Director of the FDA's Oncology Center of Excellence. "Women with these gene abnormalities who have tried at least two chemotherapy treatments for their ovarian cancer now have an additional treatment option."


Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor that blocks an enzyme involved in repairing damaged DNA. By blocking this enzyme, DNA inside the cancerous cells with damaged BRCA genes may be less likely to be repaired, leading to cell death and possibly a slowdown or stoppage of tumor growth.


The FDA also approved the FoundationFocus CDxBRCA companion diagnostic for use with rucaparib, which is the first next-generation sequencing (NGS)-based companion diagnostic approved by the agency. The NGS test detects the presence of deleterious BRCA gene mutations in the tumor tissue of ovarian cancer patients. If one or more of the mutations are detected, the patient may be eligible for treatment with rucaparib.


The diagnostic tool was developed parallel with rucaparib. Tissue samples taken from individuals with ovarian cancer who enrolled in rucaparib clinical trials were analyzed by utilizing comprehensive genomic profiling to identify biomarkers associated with a response to therapy. These molecular signatures of response informed the development of the diagnostic test, which was utilized in the pivotal trial, ARIEL2, to identify patients and accelerate recruitment into the study.


The safety and efficacy of rucaparib were studied in two, single-arm clinical trials involving 106 participants with BRCA-mutated advanced ovarian cancer who had been treated with two or more chemotherapy regimens. BRCA gene mutations were confirmed in 96 percent of tested trial participants with available tumor tissue using the companion diagnostic. The trials measured the percentage of participants who experienced complete or partial shrinkage of their tumors. Fifty-four percent of the participants who received rucaparib in the trials experienced complete or partial shrinkage of their tumors lasting a median of 9.2 months.


Common side effects of rucaparib include nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. Rucaparib is associated with serious risks, such as bone marrow problems (myelodysplastic syndrome), acute myeloid leukemia, and fetal harm.


The agency approved rucaparib under its accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease or condition based on clinical data showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. Ongoing studies of the drug are continuing in patients with advanced ovarian cancer who have BRCA gene mutations and in patients with other types of ovarian cancer.


The FDA also granted the rucaparib application breakthrough therapy designation and priority review status; rucaparib also received orphan drug designation