Novartis has received approval from the US Food and Drug Administration (FDA) for an expanded indication of Pluvicto (lutetium Lu 177 vipivotide tetraxetan), allowing its use in combination with an Androgen Receptor Pathway Inhibitor (ARPI) and Androgen Deprivation Therapy (ADT) for patients with Prostate-Specific Membrane Antigen (PSMA)-positive metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

The approval significantly broadens the use of the radioligand therapy, enabling treatment at an earlier stage of metastatic disease. Pluvicto was previously approved for patients with PSMA-positive metastatic Castration-Resistant Prostate Cancer (mCRPC). With the expanded indication, the therapy is now approved across the full spectrum of PSMA-positive metastatic prostate cancer, nearly doubling the number of patients eligible for treatment.

The FDA's decision is supported by findings from the Phase 3 PSMAddition trial, which demonstrated that adding Pluvicto to the current standard of care reduced the risk of disease progression or death by 28 percent compared with standard therapy alone. An updated analysis further strengthened the results, showing a 33 percent reduction in the risk of progression or death, while overall survival data continued to show a favourable trend for the Pluvicto combination as the study progressed toward its final analysis.

Each year, more than 186,000 men worldwide are diagnosed with metastatic hormone-sensitive prostate cancer. Although current treatment with ARPI and ADT has improved patient outcomes, many patients continue to experience disease progression. Around one-third fail to achieve undetectable Prostate-Specific Antigen (PSA) levels with existing therapy, while nearly half develop castration-resistant disease within 20 months. Since the PSMA biomarker is expressed in more than 80 percent of prostate cancers, targeted therapies such as Pluvicto have the potential to benefit a large proportion of patients.

Commenting on the approval, Dr Michael Morris, Prostate Cancer Section Head of Genitourinary Oncology at Memorial Sloan Kettering Cancer Center and a principal investigator in the US study, said the decision reflects the growing importance of introducing more intensive treatment earlier in the disease course.

Patient advocacy groups also welcomed the approval. Gina Carithers, Chief Executive Officer and President of the Prostate Cancer Foundation, described the decision as an important milestone in advancing precision medicine for prostate cancer.

The safety profile observed in the PSMAddition trial was consistent with previous clinical studies, including PSMAfore and VISION. Grade 3 or higher adverse events occurred in 50.7 percent of patients receiving Pluvicto in combination with standard therapy, compared with 43.0 percent in those receiving standard treatment alone. The most frequently reported side effects included dry mouth, fatigue, nausea, hot flushes and anemia. Health-related quality-of-life assessments remained comparable between treatment groups throughout the study.

According to Victor Bultó, President, US, Novartis, the approval represents a significant expansion of precision oncology for prostate cancer patients.

To support broader access, Novartis has expanded its radioligand therapy manufacturing network, with five production facilities operational or under construction across the United States. The company said its integrated manufacturing and logistics infrastructure enables delivery of Pluvicto to treatment centres within five days, facilitating timely treatment initiation.

Pluvicto is an intravenous radioligand therapy that combines a PSMA-targeting ligand with the radioactive isotope lutetium-177. Once administered, the therapy selectively binds to PSMA-expressing prostate cancer cells and delivers targeted radiation that damages tumour cells while limiting exposure to surrounding healthy tissue.

Beyond its approved indications, Novartis is continuing to evaluate Pluvicto in oligometastatic prostate cancer and is advancing a broader radioligand therapy pipeline encompassing new isotopes, ligands and combination approaches for multiple cancer types.