Key Takeaways:
FDA approved Novartis's Pluvicto for PSMA-positive metastatic hormone-sensitive prostate cancer, cutting progression or death risk 33%.
"Having a radioligand therapy available at this stage meaningfully expands the options for physicians and represents real progress for patients," Michael Morris, Prostate Cancer Section Head at Memorial Sloan Kettering Cancer Center and principal investigator of the study, said.
The approval is based on the Phase III PSMAddition trial, which randomized more than 1,100 patients with PSMA-positive hormone-sensitive prostate cancer. At primary analysis, Pluvicto plus standard of care (an androgen receptor pathway inhibitor and androgen deprivation therapy) reduced the risk of progression or death by 28% (HR 0.72; 95% CI: 0.58-0.90) versus standard of care alone. An updated analysis showed a 33% reduction (HR 0.67; 95% CI: 0.55-0.82) with a positive overall survival trend (HR=0.80; 95% CI: 0.63-1.01). Grade 3 or higher adverse events occurred in 50.7% of Pluvicto-treated patients versus 43.0% in the standard-of-care arm.
The approval extends Pluvicto across all stages of PSMA-positive metastatic prostate cancer, nearly doubling the eligible patient population. More than 186,000 men are diagnosed with mHSPC globally each year, and about half progress to castration-resistant disease within 20 months. The PSMA biomarker is present in more than 80% of prostate cancer patients.
Pluvicto is an intravenous radioligand therapy combining a targeting ligand with the therapeutic radionuclide lutetium-177. Once in the bloodstream, it binds to PSMA-expressing prostate cancer cells, delivering targeted radiation that disrupts replication and triggers cell death. The drug was previously approved for metastatic castration-resistant prostate cancer in both post-chemotherapy and pre-chemotherapy settings.
"This approval signals a new era in the treatment of prostate cancer, representing a shift toward more targeted, early intervention," Gina Carithers, CEO and President of the Prostate Cancer Foundation, said. "This milestone redefines prostate cancer care, ensuring that from day one of their metastatic diagnosis, men have a precision option."
The ARPI comparator arms in PSMAddition included Johnson & Johnson's Zytiga (abiraterone), Astellas/Pfizer's Xtandi (enzalutamide), Bayer's Nubeqa (darolutamide), and Johnson & Johnson's Erleada (apalutamide). Patients in both arms received a gonadotropin-releasing hormone agonist or antagonist or underwent bilateral orchiectomy.
Novartis said it has five US radioligand therapy manufacturing sites operational or under construction, with delivery to treatment sites within five days. The company's patient support program offers insurance coverage assistance and financial aid options. Novartis is also investigating Pluvicto in oligometastatic prostate cancer (PSMA-DC trial, NCT05939414).
The approval positions Pluvicto as a first-line precision option in mHSPC, expanding Novartis's radioligand therapy franchise beyond the castration-resistant setting. Investors will watch the final overall survival analysis from PSMAddition and commercial uptake in the newly approved earlier-stage indication.
This article is for informational purposes only and does not constitute investment advice.
