The FDA’s Oncologic Drugs Advisory Committee will be meeting tomorrow, Friday, 28 April, to discuss the supplemental new drug application (sNDA) for Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone for metastatic castration-resistant prostate cancer (mCRPC).
In 2017, AstraZeneca Plc AZN and Merck & Co Inc MRK collaborated to co-develop and co-commercialise Lynparza and Koselugo (selumetinib) for multiple cancer types.
Ahead of the meeting, the FDA released a briefing document and raised concerns about the safety and efficacy data. In December 2022, the agency delayed its review. It was granted Priority Review status in August 2022.
In the document, the agency pointed to a subgroup of patients without a BRCA mutation, saying that the data the companies have submitted may not be sufficient to expand use in that group.
AstraZeneca and Merck have based their application on the Phase 3 PROpel trial.
Lynparza achieved a radiographic progression-free survival of 24.8 months, compared to 16.6 months in the control group, and a 34% reduction in the risk of disease progression or death compared to the control.
But the FDA said it “is concerned that efficacy and safety have not been demonstrated outside of the small population of patients with tumor BRCA mutations and that adding olaparib to abiraterone may cause harm in patients who are definitively negative for tumor BRCA mutations.”
The FDA said the PROpel study enrolled patients whether they had BRCA status or not. In subgroup analyses, those patients with a BRCA mutation saw the most effect, “with modest benefit and possible harm for patients without tumor BRCA mutations.”
For those without a BRCA mutation, there was a five-month improvement in median radiographic progression-free survival with a hazard ratio in overall survival of 0.92.
In Q1 FY23, Lynparza generated sales of $651 million, up 50% Y/Y.
Price Action: AZN shares are down 0.01% at $73.66 on the last check Thursday.