Lutetium (177Lu) vipivotide tetraxetan

Last updated

Lutetium (177Lu) vipivotide tetraxetan
177Lu vipivotide tetraxetan -177LU-PSMA-617.svg
Clinical data
Trade names Pluvicto
Other names177Lu-PSMA-617, Lutetium Lu 177 vipivotide tetraxetan (USAN US)
License data
Routes of
administration 		Intravenous
Drug class Radiopharmaceutical
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
3D model (JSmol)
  • [177Lu+3].OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCNC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@@H]3CC[C@@H](CNC(=O)CN4CCN(CC(=O)[O-])CCN(CC(=O)[O-])CCN(CC(=O)[O-])CC4)CC3)C(=O)O)C(=O)O
  • InChI=1S/C49H71N9O16.Lu/c59-40(28-55-17-19-56(29-42(62)63)21-23-58(31-44(66)67)24-22-57(20-18-55)30-43(64)65)51-27-32-8-12-35(13-9-32)45(68)52-39(26-33-10-11-34-5-1-2-6-36(34)25-33)46(69)50-16-4-3-7-37(47(70)71)53-49(74)54-38(48(72)73)14-15-41(60)61;/h1-2,5-6,10-11,25,32,35,37-39H,3-4,7-9,12-24,26-31H2,(H,50,69)(H,51,59)(H,52,68)(H,60,61)(H,62,63)(H,64,65)(H,66,67)(H,70,71)(H,72,73)(H2,53,54,74);/q;+3/p-3/t32-,35-,37-,38-,39-;/m0./s1/i;1+2
  • Key:RSTDSVVLNYFDHY-BGOLSCJMSA-K

Lutetium (177Lu) vipivotide tetraxetan, sold under the brand name Pluvicto, is a radiopharmaceutical medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). [3] [4] Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy. [4] [6]

Contents

The most common adverse reactions include fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. [4] [5]

Lutetium (177Lu) vipivotide tetraxetan is a radioconjugate composed of PSMA-617, a human prostate-specific membrane antigen (PSMA)-targeting ligand, conjugated to the beta-emitting radioisotope lutetium-177, with potential antineoplastic activity against PSMA-expressing tumor cells. [7] Upon intravenous administration of lutetium (177Lu) vipivotide tetraxetan, vipivotide tetraxetan targets and binds to PSMA-expressing tumor cells. [7] Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. [7] PSMA, a tumor-associated antigen and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells. [7]

Lutetium (177Lu) vipivotide tetraxetan was approved for medical use in the United States in March 2022, [4] [8] and in the European Union in December 2022. [5] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. [9] [10]

History

In 2006, scientists from Purdue University designed a targeting ligand that bound with high affinity and specificity to PSMA on prostate cancer cells and patented [11] [12] its ability to target attached radionuclides such as 177Lu, 99mTc, 68Ga, etc. to prostate cancers. The patents were licensed to Endocyte in 2007. In 2012, scientists at German Cancer Research Center and University Hospital Heidelberg improved the drug's affinity, patented, [13] and licensed to ABX advanced biomedical compounds, a small German pharmaceutical company, for early clinical development. In 2017, the ABX patent was also acquired by Endocyte [14] and Endocyte together with the above two sets of patents was acquired by Novartis in 2018. [15]

Efficacy and safety was initially investigated as a compassionate access treatment in Germany with high tumor targeting and low doses to normal organs. [16] Physician-scientists from the Peter MacCallum Cancer Centre conducted a phase 2 trial demonstrating high response rates, low toxicity and reduction in pain in men with metastatic castration-resistant cancer who progressed after conventional treatments. [17] The ANZUP co-operative trials conducted the first randomized, multicentre, trial comparing lutetium vipivotide tetraxetan to cabazitaxel chemotherapy. [18] This trial demonstrated higher PSA response and fewer adverse effects with lutetium vipivotide tetraxetan.

Efficacy was evaluated in VISION, [19] a randomized (2:1), multicenter, open-label trial that evaluated lutetium (177Lu) vipivotide tetraxetan plus best standard of care (BSoC) (n=551) or BSoC alone (n=280) in men with progressive, prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). [4] All participants received a GnRH analog or had prior bilateral orchiectomy. [4] Participants were required to have received at least one androgen receptor pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. [4] Participants received lutetium (177Lu) vipivotide tetraxetan 7.4 GBq (200 mCi) every 6 weeks for up to a total of 6 doses plus BSoC or BSoC alone. [4]

The U.S. Food and Drug Administration (FDA) granted the application for lutetium (177Lu) vipivotide tetraxetan priority review and breakthrough therapy designations. [4]

Society and culture

Regulatory status

On 13 October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Pluvicto, intended for the treatment of prostate cancer. [20] The applicant for this medicinal product was Novartis Europharm Limited. [20] Lutetium (177Lu) vipivotide tetraxetan was approved for medical use in the European Union in December 2022. [5] [21]

Related Research Articles

<span class="mw-page-title-main">Prostate cancer</span> Male reproductive organ cancer

Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Early prostate cancer causes no symptoms. Abnormal growth of prostate tissue is usually detected through screening tests, typically blood tests that check for prostate-specific antigen (PSA) levels. Those with high levels of PSA in their blood are at increased risk for developing prostate cancer. Diagnosis requires a biopsy of the prostate. If cancer is present, the pathologist assigns a Gleason score, and a higher score represents a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. Higher stage signifies a more advanced, more dangerous disease.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Gallium can also be used in other forms, for example 68Ga-PSMA is used for cancer imaging. The gamma emission of gallium-67 is imaged by a gamma camera, while the positron emission of gallium-68 is imaged by positron emission tomography (PET).

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">Glutamate carboxypeptidase II</span> Enzyme

Glutamate carboxypeptidase II (GCPII), also known as N-acetyl-L-aspartyl-L-glutamate peptidase I, NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa.

<span class="mw-page-title-main">Enzalutamide</span> Antiandrogen medication used in treatment of prostate cancer

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

<span class="mw-page-title-main">Cabazitaxel</span> Chemical compound

Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid. It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy.

Sipuleucel-T, sold under the brand name Provenge, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is an autologous cellular immunotherapy.

<span class="mw-page-title-main">DOTA-TATE</span> Eight amino-acid long peptide covalently bonded to a DOTA chelator

DOTA-TATE is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator.

Endocyte is a biopharmaceutical company established in 1996 and headquartered in West Lafayette, Indiana, a resident of the Purdue Research Park. In 2011 the company completed successfully an initial public offering (IPO). As of 2013, the company had 93 employees. The original president and CEO, Ron Ellis, was succeeded by Mike Sherman, who held a CFO position at the company before this change in June 2016. In 2018 the company was acquired by Novartis.

Advanced Accelerator Applications is a France-based pharmaceutical group, specialized in the field of nuclear medicine. The group operates in all three segments of nuclear medicine to diagnose and treat serious conditions in the fields of oncology, neurology, cardiology, infectious and inflammatory diseases.

PROSTVAC is a cancer immunotherapy candidate in clinical development by Bavarian Nordic for the treatment of all prostate cancer although clinical trials are focusing on more advanced cases of metastatic castration-resistant prostate cancer (mCRPC). PROSTVAC is a vaccine designed to enable the immune system to recognize and attack prostate cancer cells by triggering a specific and targeted T cell immune response to cancer cells that express the tumor-associated antigen prostate-specific antigen (PSA).

Darolutamide, sold under the brand name Nubeqa, is an antiandrogen medication which is used in the treatment of non-metastatic castration-resistant prostate cancer in men. It is specifically approved to treat non-metastatic castration-resistant prostate cancer (nmCRPC) in conjunction with surgical or medical castration. The medication is taken by mouth twice per day with food.

<span class="mw-page-title-main">Apalutamide</span> Chemical compound

Apalutamide, sold under the brand name Erleada among others, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC). It is taken by mouth.

A PSMA scan is a nuclear medicine imaging technique used in the diagnosis and staging of prostate cancer. It is carried out by injection of a radiopharmaceutical with a positron or gamma emitting radionuclide and a prostate-specific membrane antigen (PSMA) targeting ligand. After injection, imaging of positron emitters such as gallium-68 (68Ga), copper-64 (64Cu), and fluorine-18 (18F) is carried out with a positron emission tomography (PET) scanner. For gamma emitters such as technetium-99m (99mTc) and indium-111 (111In) single-photon emission computed tomography (SPECT) imaging is performed with a gamma camera.

<span class="mw-page-title-main">Peptide receptor radionuclide therapy</span> Type of radiotherapy

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

Lutetium (<sup>177</sup>Lu) oxodotreotide Chelate of Lu-177 with DOTA-TATE, a peptide derivative bound to a DOTA molecule

Lutetium (177Lu) oxodotreotide (INN) or 177Lu DOTA-TATE, trade name Lutathera, is a chelated complex of a radioisotope of the element lutetium with DOTA-TATE, used in peptide receptor radionuclide therapy (PRRT). Specifically, it is used in the treatment of cancers which express somatostatin receptors.

<span class="mw-page-title-main">Piflufolastat F-18</span> Chemical compound

Piflufolastat F-18, sold under the brand name Pylarify among others, is a radioactive diagnostic agent used for positron emission tomography (PET) imaging. It is given by intravenous injection.

Gallium (<sup>68</sup>Ga) gozetotide Radiopharmaceutical medication

Gallium (68Ga) gozetotide or Gallium (68Ga) PSMA-11 sold under the brand name Illuccix among others, is a radiopharmaceutical made of 68Ga conjugated to prostate-specific membrane antigen (PSMA) targeting ligand, Glu-Urea-Lys(Ahx)-HBED-CC, used for imaging prostate cancer by positron emission tomography (PET). The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.

References

  1. ↑ Advanced Accelerator Applications USA. "Pluvicto Product Monograph" (PDF). The Drug and Health Product Register. Government of Canada. Retrieved 12 October 2022.
  2. ↑ "Summary Basis of Decision - Pluvicto". Health Canada. 23 October 2014. Retrieved 23 February 2023.
  3. 1 2 "Pluvicto- lutetium lu 177 vipivotide tetraxetan injection, solution". DailyMed. 23 March 2022. Archived from the original on 5 April 2022. Retrieved 4 April 2022.
  4. 1 2 3 4 5 6 7 8 9 10 "FDA approves Pluvicto for metastatic castration-resistant prostate can". U.S. Food and Drug Administration. 23 March 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. 1 2 3 4 "Pluvicto EPAR". European Medicines Agency. 12 October 2022. Retrieved 21 December 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. ↑ Neels OC, Kopka K, Liolios C, Afshar-Oromieh A (December 2021). "Radiolabeled PSMA Inhibitors". Cancers. 13 (24): 6255. doi: 10.3390/cancers13246255 . PMC   8699044 . PMID   34944875.
  7. 1 2 3 4 "Lutetium Lu 177 Vipivotide Tetraxetan (Code C148145)". NCI Thesaurus. 28 February 2022. Archived from the original on 15 April 2022. Retrieved 23 March 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. ↑ "Novartis Pluvicto approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer" (Press release). Novartis. 23 March 2022. Archived from the original on 23 March 2022. Retrieved 23 March 2022.
  9. ↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration (FDA). 10 January 2023. Retrieved 22 January 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. ↑ New Drug Therapy Approvals 2022 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 14 January 2024. Retrieved 14 January 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  11. ↑ US 11318121,Low PS, Kularatne SA,"PSMA binding ligand-linker conjugates and methods for using",issued 3 May 2022, assigned to Purdue Research Foundation
  12. ↑ US 10406240,Low PS, Kularatne SA,"PSMA binding ligand-linker conjugates and methods for using",issued 10 September 2019, assigned to Purdue Research Foundation
  13. ↑ US 20160228587,Eder M, Kopka K, Schäfer M, Bauder-Wüst U, Haberkorn U, Eisenhut M, Mier W , Benesova M,"Labeled inhibitors of prostate specific membrane antigen (psma), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer",published 11 August 2016, assigned to Deutsches Krebsforschungszentrum DKFZ, Universitaet Heidelbergand Molecular Insight Pharmaceuticals Inc.
  14. ↑ "Endocyte Announces Exclusive License of Phase 3 Ready PSMA-Targeted Radioligand Therapy for Development in Prostate Cancer". www.isotope.com. Archived from the original on 29 April 2019. Retrieved 13 April 2022.
  15. ↑ Taylor PN (18 October 2018). "Novartis inks $2.1B Endocyte buyout, furthering radiotherapy push". Fierce Biotech. Archived from the original on 30 November 2020. Retrieved 13 April 2022.
  16. ↑ Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. (November 2015). "The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions". Journal of Nuclear Medicine. 56 (11): 1697–1705. doi: 10.2967/jnumed.115.161299 . PMID   26294298. S2CID   23317879.
  17. ↑ Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. (June 2018). "[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study". The Lancet. Oncology. 19 (6): 825–833. doi:10.1016/S1470-2045(18)30198-0. PMID   29752180. S2CID   21674458.
  18. ↑ Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. (February 2021). "[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial". Lancet. 397 (10276): 797–804. doi:10.1016/s0140-6736(21)00237-3. PMID   33581798. S2CID   231885243.
  19. ↑ Clinical trial number NCT03511664 for "Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer (VISION)" at ClinicalTrials.gov.
  20. 1 2 "Pluvicto: Pending EC decision". European Medicines Agency (EMA). 13 October 2022. Archived from the original on 14 October 2022. Retrieved 14 October 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  21. ↑ "Pluvicto Product information". Union Register of medicinal products. Retrieved 3 March 2023.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.