Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan)
Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC)
Approved in the US
Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) is indicated for the treatment of progressive, prostate-specific membrane antigen-positive, metastatic, castration-resistant prostate cancer (PSMA+ mCRPC) in adult patients.
Developed by Advanced Accelerator Applications, a Novartis company, the drug is a novel targeted radioligand therapy (RLT) that is to be administered to patients pre-treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.
German radiopharmaceutical company ITM Isotopen Technologien Munchen will supply the pure medical radioisotope no-carrier-added (nca) 177Lu (EndolucinBeta®), which is a core component of Pluvicto, for the commercial-scale development of the therapy.
ITM is supplying the component under a supply agreement signed in March 2020, which aims to support the drug’s scalability and supply security, as well as future pipeline investigations of Novartis.
Pluvicto™ is available in a single-dose vial as a clear, colourless to slightly yellow solution of 1,000 megabecquerel/ml (MBq/ml) (27 millicurie (mCi)/ml) lutetium Lu 177 vipivotide tetraxetan for intravenous administration.
Regulatory approvals for Pluvicto
In March 2022, the US Food and Drug Administration (FDA) approved Pluvicto for the treatment of PSMA+ mCRPC. The FDA also approved the complementary radioactive diagnostic imaging agent Locametz (active ingredient gallium Ga 68 gozetotide) to identify PSMA+ lesions using positron emission tomography technique to select eligible patients for Pluvicto therapy.
Novartis has also submitted a marketing authorisation application for Pluvicto to the European Medicines Agency (EMA) and other regulatory health authorities.
Prostate cancer signs and symptoms
Prostate cancer occurs due to the development and growth of abnormal cells in the prostate gland.
mCRPC is an advanced form of prostate cancer that spreads beyond the prostate to other organs such as the lymph nodes, bones, bladder, rectum, and liver. The individual with mCRPC stops responding to hormone treatment known as androgen deprivation therapy (ADT).
Prostate cancer may remain asymptomatic in the early stages, while in the advanced stages, it may show signs and symptoms such as trouble in urinating, reduced force in the stream of urine, blood in urine and/or semen, pain in bone, weight loss, and erectile dysfunction.
Pluvicto’s mechanism of action
Pluvicto is a PSMA-targeted precision cancer treatment combining ligand, a targeting compound, with therapeutic radioisotope lutetium-177, a radioactive particle. PSMA is a transmembrane protein overexpressed in the majority of individuals with prostate cancer.
The ligand part of Pluvicto binds to the PSMA-expressing cells, while the beta-minus emission from lutetium-177 releases radiation to the cancer cells. This destroys their replicating ability and that of the surrounding cells, thereby triggering cell death.
Clinical trials on Pluvicto
The FDA’s approval of Pluvicto was based on the results from a randomised, multi-centre, open-label, Phase III clinical trial, VISION.
The VISION trial enrolled 831 pre-treated, progressive, PSMA+ mCRPC patients to evaluate the safety and efficacy of Pluvicto plus the best standard of care (BSoC) against BSoC alone. The patients were randomised at a 2:1 ratio to receive Pluvicto 7.4 gigabecquerel (GBq) every six weeks for a maximum of six cycles plus BSoC or BSoC alone.
The study’s primary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS).
The clinical trial showed a statistically significant improvement in both OS and rPFS in patients treated with Pluvicto plus BSoC compared with patients treated with BSoC alone. The median OS in patients treated with Pluvicto plus BSoC was 15.3 months compared with 11.3 months in the BSoC arm.
The patients treated with Pluvicto plus BSoC achieved a 38% reduction in risk of death compared with BSoC alone.
The most common adverse events reported in the trial were fatigue, dry mouth, nausea, anaemia, decreased appetite, and constipation.