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The applications are based on progression-free survival data even though the FDA has recommended that the company wait for more mature overall survival data.
Clovis Oncology has submitted a supplemental new drug application (sNDA) with the FDA and a Type II variation with the European Medicines Agency (EMA) for approval of Rubraca (rucaparib) as first-line maintenance treatment for women with advanced ovarian cancer regardless of biomarker status.
The submissions are based on positive data from the monotherapy analysis of the phase 3 ATHENA trial. These data demonstrated that Rubraca as first-line maintenance treatment significantly improved investigator-assessed progression-free survival (PFS) compared with placebo in women with advanced ovarian cancer regardless of biomarker status.
“In this analysis, rucaparib prolonged progression-free survival for patients with or without high risk factors for progression, irrespective of molecular characteristics, adding to our understanding of the efficacy of rucaparib in the broadest population of patients assessed in a clinical trial for first-line PARP inhibitor monotherapy,” Rebecca S. Kristeleit, M.D., Ph.D., of Guy’s and St. Thomas’ NHS Foundation Trust in London, said in a press release.
The study included 538 women with high-grade ovarian, fallopian tube, or primary peritoneal cancer. In the homologous recombination deficiency population, median progression-free survival for those treated with Rubraca was 28.7 months compared with 11.3 months among those who received placebo. The Rubraca arm showed statistically significant improvement over the placebo arm, representing a 53% reduction in the risk of disease progression.
In the intent-to-treat population, median progression-free survival for those treated with Rubraca was 20.2 months compared with 9.2 months for those who received placebo. The Rubraca arm showed statistically significant improvement over the placebo, representing a 48% reduction in the risk of disease progression.
The safety profile observed in ATHENA-MONO was consistent with both the current U.S. and European labels for rucaparib. The discontinuation rate due to treatment-emergent adverse events was 11.8% for rucaparib-treated patients and 5.5% for the placebo arm; there were three deaths due to TEAEs for rucaparib-treated patients.
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3. It is currently approved as a maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. It is also being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents.
The FDA has recommended that the company wait for more mature overall survival data from ATHENA-MONO to submit the sNDA. Without overall survival data, the sNDA may need to be discussed at an Oncologic Drugs Advisory Committee (ODAC) meeting.
In June, the company withdraw the indication of Rubraca in the United States as a treatment for patients with BRCA-mutated ovarian cancer after two or more chemotherapies. This did not affect other indications for Rubraca. A recent trial found that in patients with BRCA-mutated epithelial ovarian, Fallopian tubes or primary peritoneal cancer and treated with Rubraca, overall survival was shorter than with those treated with chemotherapy. The results from this trial, ARIEL4, were reported at the 2022 meeting of European Society of Medical Oncology.