The FDA has accepted a new drug application (NDA) for accelerated approval of rucaparib (Clovis Oncology) and has granted priority review status to the application with a Prescription Drug User Fee Act (PDUFA) action date of February 23, 2017.
In June 2016, Clovis completed its NDA submission of rucaparib to the FDA for the treatment of advanced ovarian cancer in patients who have deleterious BRCA-mutated tumors inclusive of both germline and somatic BRCA mutations (as detected by an FDA-approved test) and who have been treated with two or more chemotherapies. Rucaparib was granted breakthrough therapy status for the proposed indication in April 2015.
Rucaparib is an oral, small-molecule inhibitor of poly ADP ribose polymerase (PARP)-1, -2, and -3. Its efficacy was assessed in two multicenter, single-arm, open-label trials in a total of 106 patients with advanced BRCA-mutant ovarian cancer who had progressed after two or more prior chemotherapies. The patients’ median age was 59 years, and the median number of prior chemotherapy regimens was three. Study 1 was limited to platinum-sensitive patients; Study 2 included-platinum sensitive, platinum-resistant, and platinum-refractory patients. All 106 patients received a starting dosage of rucaparib 600 mg twice daily. The primary efficacy outcome measures in both trials consisted of the objective response rate (ORR) and the duration of response (DOR), as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
In Studies 1 and 2, the ORRs were 60% and 50%, respectively, and the median DORs were 7.8 months and 11.6 months. The complete response rates were 10% and 8%. The ORRs were similar for patients with germline BRCA-mutant ovarian cancer or somatic BRCA-mutant ovarian cancer, and for patients with a BRCA1 gene mutation or BRCA2 gene mutation.
According to the American Cancer Society, more than 22,000 women will be diagnosed with ovarian cancer in the U.S. during 2016. Often there are no clearly identifiable initial symptoms, and in an estimated 80% to 85% of ovarian cancer cases the cancer has metastasized before a person is diagnosed and can be treated. Ovarian cancer ranks fifth among cancer deaths and causes more deaths than any other cancer of the female reproductive system. One in four women with ovarian cancer has a germline or somatic BRCA mutation.
Source: Clovis Oncology; August 23, 2016.