Clovis Oncology's (NASDAQ:CLVS) scope with rucaparib may be limited to use in ovarian cancer patients with BRCA mutations, said experts, though rucaparib investigators were less pessimistic.
The change in the cutoff for loss of heterozygosity (LOH) led to a subdued outlook for identifying non-BRCA responders, as was earlier envisioned with the development of the LOH assay, several experts noted. However, Ariel2 investigators emphasized that that the intent of the preplanned analysis was to develop a better tool to identify responders, and refining the LOH score allowed that.
In May, before the ASCO 2016 meeting, Clovis announced its strategy to opt for an NDA that focuses on just the germline and somatic BRCA mutation (gBRCA and sBRCA) population. By selecting the gBRCA and sBRCA population, Clovis would be competing with AstraZeneca's (LON:AZN) Lynparza (olaparib) for the same patient population, with the only exception being the addition of patients with sBRCA mutations.
Companies with PARP inhibitors are exploring different strategies to expand the responder population beyond just those with gBRCA mutations. Tesaro (NASDAQ:TSRO) focused on identifying patients who didn't have gBRCA mutations but had homologous recombination deficiency (HRD) mutations in other genes that made DNA repair faulty, and Clovis used a diagnostic to identify patients where HRD would lead to a phenotype of genome-wide LOH.
Clovis plans to file a rolling NDA in 2Q16 and an MAA by 4Q16, according to analyst reports. The LOH cutoff will likely not be a part of the initial NDA submission, which will be based on BRCA mutations, but be used for the Phase III Ariel3 maintenance trial, said investigator Dr Elizabeth Swisher, professor, gynecologic oncology, University of Washington, Seattle.