US FDA Approves Pluvicto Expanded Indication for Treatment of PSMA-Positive Metastatic Hormone-Sensitive Prostate Cancer

On July 31, 2026, Novartis announced that the U.S. Food and Drug Administration (FDA) has approved Pluvicto® (lutetium Lu 177 vipivotide tetraxetan) in combination with an androgen receptor pathway inhibitor (ARPI) for the treatment of patients with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naive/sensitive prostate cancer. This disease is commonly referred to as metastatic hormone-sensitive prostate cancer (mHSPC).

The approval is based on results from the Phase III PSMAddition trial. The study showed that compared with standard of care alone, namely ARPI combined with androgen deprivation therapy (ADT), Pluvicto plus standard of care reduced the risk of disease progression or death by 28% (HR 0.72; 95% CI: 0.58–0.90). In a subsequent updated analysis, the combination reduced the risk of disease progression or death by 33% (HR 0.67; 95% CI: 0.55–0.82), and also demonstrated a favorable trend in overall survival (HR=0.80; 95% CI: 0.63–1.01), with final overall survival data still being finalized.

With this expanded indication, Pluvicto is now available for the treatment of patients with PSMA-positive metastatic prostate cancer at different stages of the disease, nearly doubling the eligible patient population. Previously, the drug was already indicated for the treatment of metastatic androgen pathway modulation-resistant prostate cancer, namely metastatic castration-resistant prostate cancer.

Data show that more than 186,000 men worldwide are diagnosed with metastatic hormone-sensitive prostate cancer each year. Despite advances in treatment, approximately one-third of patients receiving ARPI-ADT dual therapy fail to achieve undetectable PSA levels, and about half of patients progress to castration-resistant disease within 20 months. The PSMA biomarker is present in more than 80% of prostate cancer patients.

Pluvicto is an intravenously administered radioligand therapy (RLT) that combines a targeting compound with the therapeutic radionuclide lutetium-177. Once in the bloodstream, the drug binds to target cells such as PSMA-expressing prostate cancer cells; the radioisotope then releases energy that damages the target cells and their surrounding environment, impairing their ability to replicate or inducing cell death.

In terms of safety, the safety and tolerability profile of Pluvicto is consistent with that observed in the prior PSMAfore and VISION studies. In the primary analysis of PSMAddition, 50.7% of patients receiving Pluvicto plus standard of care reported grade 3 or higher adverse events, compared with 43.0% of those receiving standard of care alone. The most common adverse events included dry mouth, fatigue, nausea, hot flashes, and anemia. In the study, patients' health-related quality of life was generally maintained, with similar results across groups.

Novartis stated that the company has five radioligand therapy manufacturing sites in the United States that are either operational or under construction, and has established a system covering R&D, manufacturing, logistics, and patient support to meet treatment demand. The company is also investigating Pluvicto for the treatment of oligometastatic prostate cancer.