FDA approves Pluvicto in earlier-stage prostate cancer, expanding Novartis's radioligand franchise

The US FDA has approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) in combination with an androgen receptor pathway inhibitor (ARPI) for patients with prostate-specific membrane antigen (PSMA)-positive metastatic hormone-sensitive prostate cancer (mHSPC), extending Novartis's radioligand therapy (RLT) franchise into an earlier disease stage and making Pluvicto the only PSMA-targeted agent approved across all stages of metastatic prostate cancer. The mHSPC population is substantially larger than the previously approved metastatic castration-resistant setting, allowing treatment before progression to castration resistance.

The approval covers patients with PSMA-positive metastatic androgen pathway modulation-naive/sensitive prostate cancer, administered intravenously in combination with an ARPI plus androgen deprivation therapy (ADT). Pluvicto binds to PSMA, a transmembrane protein overexpressed on prostate cancer cells; upon binding and internalization, the lutetium-177 radioisotope emits beta particles that cause DNA double-strand breaks and tumor cell death. Patient selection requires confirmed PSMA positivity, maintaining the biomarker-driven approach established in the drug's prior mCRPC indication.

The approval is supported by the Phase III PSMAddition trial, which evaluated Pluvicto plus standard of care versus standard of care alone in PSMA-positive mHSPC patients. The primary endpoint was progression-free survival; at primary analysis, Pluvicto reduced the risk of progression or death by 28% (HR 0.72; 95% CI: 0.58–0.90). An updated analysis reported a 33% reduction (HR 0.67; 95% CI: 0.55–0.82), with an overall survival trend favoring the Pluvicto arm (HR 0.80; 95% CI: 0.63–1.01), the company said. Grade ≥3 adverse events were reported in 50.7% of patients receiving Pluvicto plus standard of care versus 43.0% on standard of care alone.

The approval expands Pluvicto into a treatment setting where ARPIs - including apalutamide (Erleada, Janssen Biotech) and darolutamide (Nubeqa, Bayer) -already provide established overall survival benefits, positioning the radioligand as an add-on rather than a replacement therapy. In the broader PSMA-targeted RLT pipeline, AdvanCell's lead-212 alpha-emitting radioligand therapy ADVC001 is advancing into Phase III for metastatic prostate cancer, representing a next-generation modality in the same target space.

Novartis said the mHSPC approval nearly doubles the eligible patient population for Pluvicto compared with its mCRPC indication alone. The company reported five US RLT manufacturing sites now operational or under construction, with a stated delivery window of five days to US treatment sites.

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