FDA Advisory Committee Votes Against Accelerated Approval for AstraZeneca Cancer DrugBy
AstraZeneca reports that the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 11 to 2 that current evidence from clinical studies does not support an accelerated approval for use of olaparib as a maintenance treatment for women with platinum-sensitive relapsed ovarian cancer who have the germline BRCA (gBRCA) mutation and who are in complete or partial response to platinum-based chemotherapy.
Olaparib is an investigational oral poly ADP ribose polymerase (PARP) inhibitor that exploits tumor DNA repair pathway deficiencies to selectively induce cancer cell death. This mode of action gives olaparib the potential for activity in a range of tumor types with DNA repair deficiencies.PARP is a key enzyme in one of the DNA repair pathways in human cells. Inhibition of PARP results in a build-up of DNA damage in the cell, requiring repair via an alternative pathway called Homologous Recombination repair (HR). Cancer cells that already have a HR pathway deficiency (HRD) are limited in their ability to repair their DNA, overloading them with DNA damage and causing them to die. A number of abnormalities can cause HRD in cancer cells, including BRCA gene mutations. HRD is associated with a range of tumor types, in particular with breast and ovarian cancers.
In addition to ovarian cancer, olaparib is being investigated in combination with chemotherapy in second-line gastric cancer, and Phase III studies are evaluating olaparib in adjuvant and metastatic breast cancer with BRCA mutations.
The ODAC provides the FDA with independent, expert advice and recommendations; however, the final decision regarding approval is made by the FDA. AstraZeneca filed the US regulatory submission for olaparib in February 2014. The FDA granted priority review status for the new drug application in April and set a Prescription Drug User Fee Act action date of October 3, 2014.