At the FDA’s request, GSK has restricted the use of Zejula, a PARP inhibitor, to a specific population as a second-line maintenance treatment for ovarian cancer following updated data.
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At the FDA’s request, GSK has restricted the use of Zejula, a PARP inhibitor, to a specific population as a second-line maintenance treatment for ovarian cancer following updated Phase III data.
The drug will be restricted to only the patient population with deleterious or suspected deleterious germline BRCA mutations (gBRCAmut). The company announced its decision Friday after a review of overall survival data from the Phase III ENGOT-OV16/NOVA study, which was studying the drug for the maintenance treatment of women with platinum-sensitive recurrent ovarian cancer.
Upon a final examination of data, GSK said the secondary endpoint of overall survival demonstrated a hazard ratio of 1.06 in the non-gBRCAmut cohort, leading to a 10% greater risk of death.
Zejula’s first-line indication as a maintenance treatment for adult patients diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who have had a complete or partial response to platinum-based chemotherapy remains unchanged.
A GSK spokesperson told BioSpace there is no change to the benefit/risk profile of Zejula in the non-gBRCAm patient population. The spokesperson also said GSK will comply with the FDA’s request to restrict the second-line indication to the gBRCAm subset of patients in the U.S.
The primary endpoint of the NOVA study was progression-free survival in cohorts of patients with and without gBRCAmut mutation. In both cohorts, Zejula demonstrated a clinically meaningful and statistically significant benefit. Secondary endpoints were safety and long-term exploratory endpoints, including overall survival.
GSK is engaging in discussions about these data points with health authorities worldwide.
The FDA’s Oncologic Drugs Advisory Committee was set to meet later in November to discuss the NOVA data, but the meeting was canceled after the FDA said it was no longer needed.
This latest restriction for Zejula follows GSK’s decision to pull the use of the PARP inhibitor in the fourth-line treatment of patients with advanced ovarian, fallopian tube or primary peritoneal cancers whose disease is associated with homologous recombination deficiency (HRD) positive status.
The withdrawal of the use of Zejula in that indication was made in consultation with the FDA, based on what GSK said was a “totality of information from PARP inhibitors in the late line treatment setting in ovarian cancer.”
In a September note to prescribers, GSK said there was an observed detrimental effect on overall survival from PARP inhibitors not developed by GSK in two clinical trials conducted in a third-line ovarian cancer patient population who have BRCA mutant disease.
GSK’s Zejula has been one of many PARP inhibitors subjected to post-approval scrutiny. AstraZeneca’s and Merck’s Lynparza and Clovis Oncology’s Rubraca have also been put under the microscope as a late-line treatment option in ovarian cancer with the BRCA mutation.
In September, AstraZeneca withdrew Lynparza from use as a treatment for highly pre-treated patients with advanced ovarian cancer with a BRCA mutation. That decision was based on an overall survival analysis of data from the Phase III SOLO3 study that showed patients treated with Lynparza had a 33% greater risk of death than control patients.
Likewise, Clovis pulled the use of Rubraca in the U.S. for third-line ovarian cancer patients with the BRCA mutation.
