Negative FDA briefing docs for Lynparza

The US Food and |Drug Administration (FDA) has released briefing documents for the April 28, 2023, Advisory Committee Meeting (AdCom) discussing the supplemental new drug application (sNDA) for UK AstraZeneca’s (LSE: AZN) Lynparza (olaparib) in first-line (1L) metastatic castration-resistant prostate cancer (mCRPC).

Overall, the briefing documents suggest strong headwinds for Lynparza to gain approval beyond BRCA+ patients, which potentially represents just ~11% of the addressable 1L market. The key concern of the agency, consistent with that noted in other tumor types and with other PARP inhibitors, is whether Lynparza should be used in patients that do not have a BRCA+ deficiency.

The documents highlight that the trial did not have prospectively defined, clinically meaningful biomarker analyses or stratification of repair deficiencies, but the agency conducted subsequent evaluations of both the PROPEL trial and Study 8, finding that the primary driver of efficacy benefit was in BRCA mutated patients, and that non-BRCA patients had a "potentially detrimental rPFS and [overall survival] OS."