Pfizer has announced that the US Food and Drug Administration (FDA) has accepted for Priority Review its supplemental New Drug Application (sNDA) for TALZENNA® (talazoparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with XTANDI® (enzalutamide) for the treatment of adults with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations. Priority Review designation shortens the FDA review timeline for therapies that may provide significant improvements in the treatment of serious diseases, underscoring the potential clinical importance of this combination in an area of unmet need.
The application is based on results from the global, randomized, double-blind Phase 3 TALAPRO-3 trial, which evaluated TALZENNA plus XTANDI versus placebo plus XTANDI in patients with HRR gene-mutated mCSPC. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS). Treatment with the combination significantly delayed disease progression or death compared with XTANDI alone, supporting the potential benefit of introducing PARP inhibition earlier in the disease course.
The safety profile of TALZENNA plus XTANDI was generally consistent with the known safety profiles of the individual agents and with previous clinical experience in advanced prostate cancer. No unexpected safety signals were identified. The findings suggest that combining targeted DNA damage repair inhibition with androgen receptor pathway inhibition may offer improved disease control for patients whose tumors harbor HRR gene alterations, including mutations in BRCA1, BRCA2, ATM, and other DNA repair genes.
TALZENNA is currently approved in combination with XTANDI for the treatment of adults with homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer (mCRPC). If approved, the new indication would expand the use of the combination into the earlier metastatic castration-sensitive setting, enabling eligible patients to receive precision-targeted therapy before progression to castration-resistant disease. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date in the second half of 2026. The Priority Review reflects the growing role of biomarker-guided treatment strategies in prostate cancer and represents a potential advance in improving outcomes for patients with HRR gene-altered metastatic disease.
