Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto)

Pluvicto is this site's second peptide-receptor radionuclide therapy, after Lutathera — but instead of targeting the somatostatin receptor on neuroendocrine tumors, it targets prostate-specific membrane antigen (PSMA) on prostate cancer cells. FDA-approved in March 2022 on a real, mortality-benefit Phase 3 trial, it then went through a genuine 2022-2023 supply crisis before two later trials expanded it into progressively earlier stages of the disease, most recently in July 2026.

A radioligand aimed at a different target than Lutathera

Pluvicto's active ingredient is vipivotide tetraxetan — a small-molecule, peptide-like ligand (also known by its research name, PSMA-617) that binds prostate-specific membrane antigen, a protein overexpressed on the surface of most prostate cancer cells — chelated to lutetium-177, the same beta-emitting radioisotope used in Lutathera. The underlying mechanism is the same peptide-receptor radionuclide therapy (PRRT) principle this site already covers through Lutathera: use a receptor the tumor overexpresses as an address label, then let the attached radioisotope do the actual killing. But the target protein, the disease, and the developer are all different — PSMA instead of the somatostatin receptor, prostate cancer instead of neuroendocrine tumors, and Novartis's Advanced Accelerator Applications unit developing this one in-house rather than acquiring an already-approved product. The FDA approved it on 23 March 2022 for adults with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had already been treated with an androgen receptor pathway inhibitor and taxane-based chemotherapy.

VISION: the trial that got it approved

The pivotal VISION trial randomized 831 patients with progressive, PSMA-positive mCRPC, 2:1, to either Pluvicto plus protocol-permitted standard of care or standard of care alone. Median overall survival was 15.3 months with Pluvicto versus 11.3 months on standard of care alone, a hazard ratio of 0.62 (p<0.001) (Sartor O, de Bono J, Chi KN, et al., for the VISION Investigators, "Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer," N Engl J Med 2021;385(12):1091-1103, PMID 34161051, DOI: 10.1056/NEJMoa2107322).¹ Median radiographic progression-free survival — the trial's other primary endpoint — improved from 3.4 to 8.7 months (HR 0.40, p<0.001). That's a real, statistically decisive survival benefit in an adequately powered, randomized trial, not a surrogate-endpoint-only result, and it's the basis of the FDA's traditional (not accelerated) approval.

A genuine supply crisis, and how it was resolved

Demand for Pluvicto outstripped Novartis's manufacturing capacity almost immediately after launch, and by mid-2022 the FDA's drug shortage database listed it as a confirmed shortage — patients in active treatment were being turned away or delayed between cycles, a genuinely serious problem for a drug given on a fixed six-week schedule. Novartis responded by more than doubling weekly production capacity between May and October 2023, adding commercial manufacturing capability at a New Jersey (Millburn) facility and building a new radioligand-therapy plant in Indianapolis, alongside existing production in Ivrea, Italy and Zaragoza, Spain. The FDA classified the shortage as resolved in October 2023, and Novartis has since described supply as unconstrained while continuing to expand treatment-center access. It's a real supply-chain failure that actually got fixed with capital investment, not one that was quietly written off.

Moving earlier: PSMAfore and PSMAddition

Two later Phase 3 trials pushed Pluvicto into progressively earlier disease stages. The PSMAfore trial randomized 468 taxane-naive mCRPC patients who had progressed on one androgen receptor pathway inhibitor to either Pluvicto or a change to a different pathway inhibitor, finding a 51% reduction in the risk of radiographic progression or death (HR 0.49) (Morris MJ, de Bono JS, Chi KN, et al., "177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial," Lancet 2024;404(10459):1227-1239, PMID 39293462, DOI: 10.1016/S0140-6736(24)01653-2).² That result supported an FDA label expansion on 28 March 2025 to taxane-naive mCRPC patients considered appropriate to delay chemotherapy — roughly tripling the pool of eligible patients. A second trial, PSMAddition, moved further still, testing Pluvicto added to standard hormonal therapy in patients who hadn't yet become castration-resistant at all (metastatic hormone-sensitive prostate cancer, mHSPC): topline results presented at ESMO and SUO in 2025 showed a 33% reduction in progression-or-death risk (HR 0.67) with a favorable overall-survival trend, later published in full (Tagawa ST, Sartor O, et al., "[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial," Lancet 2026, DOI: 10.1016/S0140-6736(26)01092-5).³ The FDA approved this mHSPC combination indication on 31 July 2026 — this site's most recently approved indication for any drug it covers.

Current status

Novartis markets Pluvicto worldwide and has continued expanding both manufacturing capacity and the number of certified treatment centers able to administer it since the 2023 shortage resolved. It remains restricted to patients whose tumors are confirmed PSMA-positive by dedicated PET imaging (with a companion diagnostic, Locametz/Illuccix), administered exclusively at licensed nuclear-medicine facilities under the same radiopharmaceutical handling and patient radiation-safety precautions described on this site's Lutathera page. There is no outpatient, wellness or grey-market version of this drug in any form — a radioactive infusion requires a licensed facility by definition.