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Pluvicto (Lutetium (177Lu) vipivotide tetraxetan)
Australian Prescription Medicine Decision Summary
ARTGs
Device/Product name
Pluvicto
Active Ingredient
Lutetium (177Lu) vipivotide tetraxetan
Date of decision
Published
Submission type
Type A - New chemical entity
ATC codes
V10XX05 (V10 THERAPEUTIC RADIOPHARMACEUTICALS)
Decision
Approved
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor.
The registration of Pluvicto in mCRPC is primarily based on the efficacy demonstrated in patients with progressive, prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer (mCRPC) established in the VISION trial, a randomised, multicenter, open-label Phase III study. 831 patients were randomised to receive either Pluvicto every 6 weeks for up to a total of 6 doses plus best standard of care (BSoC) or BSoC alone. Treatment with Pluvicto plus BSoC demonstrated a statistically significant improvement in overall survival and radiographic progression-free survival compared to treatment with BSoC alone.
The registration of Pluvicto in mCRPC is primarily based on the efficacy demonstrated in patients with progressive, prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer (mCRPC) established in the VISION trial, a randomised, multicenter, open-label Phase III study. 831 patients were randomised to receive either Pluvicto every 6 weeks for up to a total of 6 doses plus best standard of care (BSoC) or BSoC alone. Treatment with Pluvicto plus BSoC demonstrated a statistically significant improvement in overall survival and radiographic progression-free survival compared to treatment with BSoC alone.
What steps were involved in the decision process
This submission was evaluated under the standard prescription medicines registration process
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 1 August 2023 |
| Evaluation completed | 15 April 2023 |
| Delegate’s1 Overall benefit-risk assessment and request for Advisory Committee advice | 6 May 2024 |
| Sponsor’s pre-Advisory Committee response | 16 May 2024 |
| Advisory Committee meeting | 20 June 2024 |
| Registration decision (Outcome) | 16 July 2024 |
| Administrative activities and registration in the ARTG completed | 17 July 2024 |
| Number of working days from submission dossier acceptance to registration decision2 | 244 |
1The ‘Delegate’ is the Delegate of the Secretary of the Department of Health and Aged Care who made the final decision to either include the new medicine/indication on the ARTG or reject the submission, under section 25 of the Therapeutic Goods Act..
2Statutory timeframe for standard submissions is 255 working days
Date of entry onto ARTG
Black triangle scheme
Pluvicto is to be included in the Black Triangle Scheme. The PI and CMI for Pluvicto must include the black triangle symbol ▼ for five years. The black triangle is a visual reminder to encourage health practitioners and patients to report a problem or side effect with this medicine.
Dose forms
Pluvicto is a clear, colourless to slightly yellow solution
Strength
One mL of solution contains 1,000 Megabecquerel (MBq; a unit of ionizing radiation exposure) of lutetium (177Lu) vipivotide tetraxetan at the date and time of calibration.
Other ingredients
Acetic acid, sodium acetate, gentisic acid, sodium ascorbate, pentetic acid, water for injections.
Containers
Pluvicto is supplied in a clear, colourless type I glass vial, closed with a bromobutyl rubber stopper and aluminum seal.
Each vial contains a volume of solution that can range from 7.5 mL to 12.5 mL corresponding to a radioactivity of 7,400 MBq ± 10% at the date and time of administration.
The vial is enclosed within a lead container for protective shielding.
Each vial contains a volume of solution that can range from 7.5 mL to 12.5 mL corresponding to a radioactivity of 7,400 MBq ± 10% at the date and time of administration.
The vial is enclosed within a lead container for protective shielding.
Routes of administration
Intravenous injection
Dosage
The recommended Pluvicto dose is 7,400 MBq intravenously every 6 weeks (± 1 week) for up to a total of 6 doses or until disease progression, or unacceptable toxicity.
Pregnancy category
X: Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy.
What was approved
Pluvicto (Lutetium (177Lu) vipivotide tetraxetan) has been approved for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.
What is this medicine and how does it work
The active ingredient in Pluvicto is the radionuclide lutetium-177 (a radionuclide is a chemical that has an unstable atomic nucleus and as a result emits radiation). The radionuclide is linked to a molecule that targets it to PSMA, a protein that is highly expressed on prostate cancer cells, including metastatic castration-resistant prostate cancer cells. Upon binding of Pluvicto to PSMA-expressing cancer cells, lutetium-177 delivers therapeutic radiation to the targeted cell, as well as to surrounding cells, and induces DNA damage which can lead to the death of the cancer cells.
What post-market commitments will the sponsor undertake
Pluvicto is to be included in the Black Triangle Scheme. The PI and CMI for Pluvicto must include the black triangle symbol and mandatory accompanying text for five years. The Black Triangle Scheme identifies new prescription medicines with a black triangle on the medicine information documents. The black triangle is a visual reminder to encourage health practitioners and patients to report a problem or side effect associated with this medicine.
RMP Conditions
The PLUVICTO EU-Risk Management Plan (RMP) (version 1.2, dated 11 October 2022, and, DLP 27 January 2021), with Australian Specific Annex (version 1.0, dated 20 June 2023), included with submission PM-2023-02254-1-4, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).
Reports are to be provided in line with the current published list of EU reference dates and frequency of submission of PSURs until the period covered by such reports is not less than three years from the date of this approval letter. Each report must be submitted within ninety calendar days of the data lock point for that report.
The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency’s Guideline on good pharmacovigilance practices (GVP) Module VII-periodic safety update report (Rev 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.
Conduct an integrated safety analysis to further characterize the long term outcome of the known serious risk of myelosuppression, renal failure, xerostomia and xerophthalmia and their complications; the potential serious signals of secondary malignancies including myelodysplastic syndrome and acute myeloid leukemia (MDS/AML); and other serious adverse reactions in patients receiving lutetium (177Lu) vipivotide tetraxetan in the VISION study and its sub-study, Trial CAAA617C12301 (NCT04720157), Trial CAAA617B12302 (NCT04689828) and other clinical trials as appropriate. Capture data prospectively in amended case report forms to include incidence, grade, date of onset and resolution of the adverse reaction, predisposing factors and outcomes, date and quantity of red cell and platelet transfusion, use of growth factors for myelosuppression, subsequent antineoplastic therapies, radiation therapy, and hospital admissions. Follow all patients until death, loss to follow-up, or for up to 10 years, whichever occurs first.
Conduct a clinical trial to determine the kidney biodistribution, dosimetry, pharmacokinetics, and safety of lutetium (177Lu) vipivotide tetraxetan and assess the potential for higher drug exposure and the resultant risk of increased serious toxicities in patients with moderate and severe renal impairment. Assess long-term toxicities in these patients. Follow all patients until death, loss to follow-up, or for up to 10 years, whichever occurs first. Include risk mitigation strategies to reduce potential toxicities in the final report. Design and conduct the trial in accordance with FDA Guidance for Industry titled Pharmacokinetics in Patients with Impaired Renal Function: Study Design, Data Analysis, and Impact on Dosing.
Conduct a clinical trial to evaluate the efficacy and safety of lutetium (177Lu) vipivotide tetraxetan in patients with advanced/metastatic prostate cancer who have at least one lesion with PSMA expression higher than that in normal liver parenchyma on PSMA-11 PET scan and at least one lesion with PSMA expression less than or equal to uptake in normal liver, with the following size criteria in short axis: size criteria in short axis: organs >1 cm, lymph nodes >2.5 cm, bones (soft tissue component) >1cm. Alternatively, add cohorts of these patients to ongoing trials. Include an analysis of these safety and efficacy data.
More information
The latest Product Information (PI) and Consumer Medicine Information (CMI) can be found by searching the Australian Register of Therapeutic Goods (ARTG).
Australian Public Assessment Reports (AusPARs) can be found by searching our AusPAR dataset.
The latest news and updates regarding therapeutic goods regulation can be found on our news page.