FDA panel rebuffs olaparib

FDA's Oncologic Drugs Advisory Committee voted 11-2 that safety and efficacy data do not support accelerated approval of olaparib from AstraZeneca plc (LSE:AZN; NYSE:AZN) and that the agency should delay considering approval until results are available from an ongoing confirmatory Phase III trial. AZ is seeking accelerated approval of the poly(ADP-ribose) polymerase (PARP) inhibitor as maintenance treatment of platinum-sensitive relapsed ovarian cancer in patients with germline breast cancer early onset (BRCA) mutations who are responding to platinum-based chemotherapy.

AZ's application is based on a Phase II trial (Study 19) in which that subgroup of patients showed a 7.1-month progression-free survival (PFS) benefit with olaparib vs. placebo. ODAC panelists were concerned this difference was unreliable because it came from a small set of patients whose BRCA mutations were identified retrospectively, which both FDA and panelists said may have compromised randomization. Panelists also said olaparib's side effects, including a risk of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), might offset the potential benefits of increased PFS. ...