FDA Grants Accelerated Approval to Rubraca for BRCA-positive Advanced Ovarian Cancer

FDA Grants Accelerated Approval to Rubraca for BRCA-positive Advanced Ovarian Cancer

The U.S. Food and Drug Administration (FDA) granted accelerated approval to Clovis Oncology’s drug candidate Rubraca (rucaparib) to treat women with BRCA-positive advanced ovarian cancer, who have been treated with two or more chemotherapies.

“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,”  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, said in a press release. “Women with these gene abnormalities who have tried at least two chemotherapy treatments for their ovarian cancer now have an additional treatment option.”

According to the National Cancer Institute, about 15 percent to 20 percent of patients with ovarian cancer have a BRCA gene mutation.

Rubraca is a poly ADP-ribose polymerase (PARP) inhibitor with potential as an anti-cancer agent, that targets the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). BRCA genes are required for normal DNA repair mechanisms, and as such, by blocking this enzyme, the DNA inside cancerous cells with damaged BRCA genes is less likely to be repaired, causing the cells to die and, possibly, slowing tumor growth. BRCA mutations are considered particularly deleterious.

The FDA also approved the FoundationFocus CDxBRCA companion diagnostic test to be used with Rubraca. The FoundationFocus CDxBRCA was co-developed by Clovis and Foundation Medicine to select patients for Rubraca treatment. A tissue-based, genomic assay, it detects BRCA1 and BRCA2 mutations (germline, meaning inherited, or somatic, meaning acquired) in ovarian cancer tissue.

Approval of Rubraca and the FoundationFocus CDxBRCA test was based on the results of two multicenter, open-label and single-arm clinical trials that evaluated the safety and efficacy of Rubraca in 106 patients with advanced ovarian cancer, whose disease had progressed after treatment with two or more chemotherapies. Single-arm trials have no placebo group, so all patients receive the investigative therapy.

BRCA1/2 status was determined in 96 percent of the patients with the FoundationFocus CDxBRCA assay, using tumor tissue  samples. The trial measured the number of Rubraca-treated patients who experienced complete or partial shrinkage of their tumors (overall response rate). Complete or partial responses lasting a median 9.2 months were observed in 54 percent of the patients.

Side effects that are common to Rubraca include fatigue, nausea, vomiting, constipation, abdominal pain, low levels of red blood cells (anemia), diarrhea, unusual taste sensation (dysgeusia), decreased appetite, low levels of blood platelets (thrombocytopenia) and trouble breathing (dyspnea), the FDA noted in its release.  Rubraca may cause bone marrow problems, fetal harm, and other serious complications.

The FDA decision on Rubraca came under its accelerated approval program, which allows the approval of a drug meant to treat a serious disease based on a surrogate endpoint. Clovis will continue to evaluate Rubraca in the same patient population, as well as in patients with other types of ovarian cancer, to further support Rubraca’s approval.

Rubraca also holds the FDA’s breakthrough therapy designation, priority review status, and orphan drug designation.

Clovis has also applied to the European Union for Rubraca to treat BRCA-positive advanced ovarian cancer patients in those countries.