The FDA has granted Priority Review for the niraparib New Drug Application (NDA). Niraparib is a PARP inhibitor that is being evaluated as a potential new treatment option for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer following response to platinum-based chemotherapy. The FDA has established a target action date under the Prescription Drug User Fee Act of June 30, 2017, and is not currently planning to hold an advisory committee meeting to discuss this application.
The niraparib NDA is supported by data from the ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international phase III study that enrolled 553 patients with recurrent ovarian cancer who had achieved either a partial response or a complete response to their most recent platinum-based chemotherapy. This trial was designed to assess progression-free survival (PFS) in patients who were assigned to one of two cohorts based upon germline BRCA mutation status. The full results of the ENGOT-OV16/NOVA trial were presented in detail at the European Society for Medical Oncology 2016 Congress and were published simultaneously in The New England Journal of Medicine (doi: 10.1056/NEJMoa1611310).
The ENGOT-OV16/NOVA trial successfully achieved its primary endpoint in both patient cohorts, demonstrating that niraparib treatment significantly prolonged PFS compared to control. Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.27 (95% CI, 0.173-0.410). The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p<0.0001). Among patients in the non-germline BRCA mutant cohort, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS, with a hazard ratio of 0.45 (95% CI, 0.338-0.607). The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p<0.0001). Based upon the results of this trial, the indication proposed in the NDA provides for the use of niraparib regardless of tumor biomarker status.
The most common (>=10%) treatment-emergent grade 3/4 adverse events in the niraparib arm were thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%) with treatment discontinuation for these events of 3.3 percent, 1.4 percent, and 1.9 percent, respectively. Thrombocytopenia was not associated with grade 3/4 bleeding events. The majority of these hematological laboratory abnormalities occurred within the first three cycles; following dose modifications based on individual patient tolerability, the incidence of these lab abnormalities decreased and thrombocytopenia and neutropenia were infrequent beyond cycle 3. The rates of MDS/AML in the niraparib (1.4%) and control (1.1%) arms were similar. There were no deaths among patients during study treatment.
An Expanded Access Program for niraparib in the U.S. is planned to open in January 2017. Through the program, niraparib will be made available for patients with recurrent ovarian cancer following response to platinum-based chemotherapy.