Clovis Oncology, Inc. announced that it has submitted a supplemental New Drug Application (sNDA) with the US Food and Drug Administration (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 who have responded to first-line platinum-based chemotherapy. The Company believes that the encouraging PFS results, the primary endpoint of the study, are strongly supportive of an approval and of use in the front-line setting and are grateful for the support of the clinical community familiar with the results. The submissions were based on the positive data from the monotherapy analysis of the randomized, Phase 3 ATHENA (GOG-3020/ENGOT-ov45) trial (ATHENA-MONO).

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 irrespective of biomarker status in each of the populations studied. The ATHENA-MONO study included 538 women with high-grade ovarian, fallopian tube, or primary peritoneal cancer. The primary efficacy analysis evaluated two prospectively defined molecular populations in a step-down manner: homologous recombination deficiency (HRD)1 positive (inclusive of BRCAm tumors and BRCAwt/LOH high tumors); and all patients randomized (ITT) in the trial.

The primary endpoint for the trial was PFS by investigator review. In the HRD population, median PFS by investigator review for those treated with Rubraca was 28.7 months compared to 11.3 months among those who received placebo (p=0.0004). The Rubraca arm (n=185) showed statistically significant improvement over the placebo arm (n=49) with a hazard ratio of 0.47 (95% CI: 0.31-0.72) representing a 53% reduction in the risk of disease progression.

In the ITT population, median PFS by investigator review for those treated with Rubraca was 20.2 months compared to 9.2 months for those who received placebo (p<0.0001). The Rubraca arm (n=427) showed statistically significant improvement over the placebo arm (n=111) with a hazard ratio of 0.52 (95% CI: 0.40-0.68) representing a 48% reduction in the risk of disease progression. The safety profile observed in ATHENA-MONO was consistent with both the current US and European labels for rucaparib.

The most common (=2%) treatment-emergent grade =3 adverse events (TEAEs) among all patients treated with rucaparib (n=425) in the ATHENA-MONO comparison were anemia or decreased hemoglobin (28.7%), neutropenia or neutrophil count decreased (14.6%), increased ALT/AST (10.6%), thrombocytopenia or platelet count decreased (7.1%), asthenia/fatigue (4.9%), and leukopenia/white blood cell count decreased (3.5%). AST/ALT elevations were not accompanied by significant changes in bilirubin and there were no reports of drug induced liver toxicity as defined by Hy's Law. The discontinuation rate due to TEAEs was 11.8% for rucaparib-treated patients and 5.5% for the placebo arm; there were three deaths (0.7%) due to TEAEs for rucaparib-treated patients and zero for the placebo arm.

Median treatment duration for the rucaparib arm was 14.7 months versus 9.9 months for the placebo arm. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) was reported by two patients in the rucaparib group (one MDS during treatment; one AML during long-term follow-up) and no patients in the placebo group. As previously disclosed, the FDA has recommended that the Company wait for more mature overall survival data from ATHENA-MONO to submit the sNDA or, if it chooses to submit the sNDA prior to receiving more mature overall survival data, then the sNDA may need to be discussed at an Oncologic Drugs Advisory Committee (ODAC) meeting.

In addition, the FDA will consider overall survival data from other rucaparib clinical trials when it reviews the ATHENA-MONO dataset. Not all rucaparib overall survival data has been submitted to the FDA nor is all data currently public. There can be no assurances regarding the timing or outcome of the FDA and EMA reviews of the submissions, nor, if approved, the scope of the resulting label.

Rubraca is not currently approved in the first-line ovarian cancer maintenance setting.