FDA Approves Novartis' Pluvicto for Use in Prostate Cancer Prior to Chemotherapy
Approval Scope and Treatment Sequence
On March 28, 2025, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) from Novartis AG (NVS) for use in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) after treatment with an androgen receptor pathway inhibitor (ARPI), allowing for the postponement of taxane-based chemotherapy. This is not an approval for the simultaneous administration of Pluvicto and an ARPI, but rather an expansion of the indication to allow for Pluvicto to be used after ARPI therapy. As a result, the treatment sequence has shifted to an earlier stage, before chemotherapy.
Drug and Clinical Evidence
Pluvicto is a targeted radioligand therapy that binds to prostate-specific membrane antigen (PSMA) and delivers beta radiation from lutetium-177 to the tumor. The approval is based on the Phase 3 PSMAfore (NCT04689828) trial, which randomized 468 patients who had progressed after one cycle of ARPI therapy to receive either Pluvicto or a change in ARPI therapy in a 1:1 ratio. The median radiographic progression-free survival (rPFS), as assessed by an independent central review, was 9.3 months in the Pluvicto group and 5.6 months in the ARPI change group, with a hazard ratio of 0.41, a 95% confidence interval of 0.29 to 0.56, and a p-value of less than 0.0001. The median overall survival was 24.5 months in the Pluvicto group and 23.1 months in the ARPI change group, which did not reach statistical significance, and 60% of patients in the control group crossed over to receive Pluvicto after progression.
Competitive Landscape and Safety
Existing treatment options include switching to another ARPI, such as Xtandi (enzalutamide) or Zytiga (abiraterone acetate), taxane-based chemotherapy, such as docetaxel or cabazitaxel, or Xofigo (radium Ra 223 dichloride) for patients with bone metastases. This data demonstrates the superiority of switching to a PSMA-targeted mechanism compared to switching to another ARPI in the same class, which will directly impact the treatment algorithm. However, due to the risk of radiation exposure, bone marrow suppression, and nephrotoxicity, the availability of hematological and renal function monitoring, as well as radiopharmaceutical administration infrastructure, will be key factors in determining the actual rate of adoption.
Regulatory and Market Implications
Pluvicto was first approved by the FDA in March 2022 for use in mCRPC after chemotherapy, and it received marketing authorization in the European Union on December 9, 2022. The 2025 U.S. indication expansion review utilized the FDA Assessment Aid, and the approval announcement did not include an advisory committee (AdComm) vote. Novartis' Pluvicto sales in 2025 were USD 1.994 billion, a 43% increase year-over-year, and it has already achieved blockbuster status. Including patients before chemotherapy will increase the potential duration and number of patients who can receive the treatment, but PSMA-PET screening capabilities and the ability to produce and deliver isotopes will be key factors limiting sales growth.
This approval is commercially significant because it moves Pluvicto to an earlier stage of treatment, based on the Phase 3 PSMAfore trial, which showed a 59% reduction in the risk of rPFS compared to switching to another ARPI. Novartis AG (NVS) recorded Pluvicto sales of USD 1.994 billion in 2025, and the expansion of the indication will broaden the treatment population and timing. In competition with docetaxel, cabazitaxel, Xtandi, Zytiga, and Xofigo, both efficacy and access to PSMA-PET, radiopharmaceutical production capacity, and management of bone marrow toxicity will determine market share. An increase in U.S. prescriptions is expected in the short term, but long-term evaluation will depend on the maturation of overall survival data and the potential for further expansion of treatment to earlier stages through the Phase 3 PSMAddition trial in mHSPC.