Lutetium (177Lu) vipivotide tetraxetan explained

Drug Name:Lutetium (177Lu) vipivotide tetraxetan
Usan:Lutetium Lu 177 vipivotide tetraxetan
Tradename:Pluvicto
Dailymedid:Pluvicto
Routes Of Administration:Intravenous
Class:Radiopharmaceutical
Atc Prefix:V10
Atc Suffix:XX05
Legal Ca:Rx-only
Legal Ca Comment:/Schedule C[1] [2]
Legal Us:Rx-only
Legal Us Comment:[3]
Legal Eu:Rx-only
Legal Eu Comment:[4]
Cas Number:1703749-62-5
Pubchem:122706785
Drugbank:DB16778
Chemspiderid:58828499
Unii:G6UF363ECX
Kegg:D12335
Synonyms:177Lu-PSMA-617
Smiles:[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
Stdinchi: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
Stdinchikey: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).[5] Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.[6]

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

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. Upon intravenous administration of lutetium (177Lu) vipivotide tetraxetan, it targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. 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,[8] and in the European Union in December 2022. 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). All participants received a GnRH analog or had prior bilateral orchiectomy. Participants were required to have received at least one androgen receptor pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. 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.

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

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. 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.[21]

External links

Notes and References

  1. Web site: Advanced Accelerator Applications USA . Pluvicto Product Monograph . The Drug and Health Product Register . Government of Canada . 12 October 2022.
  2. Web site: Summary Basis of Decision - Pluvicto . Health Canada . 23 October 2014 . 23 February 2023 . 24 February 2023 . https://web.archive.org/web/20230224043105/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00621&lang=en . dead .
  3. Web site: Pluvicto- lutetium lu 177 vipivotide tetraxetan injection, solution . DailyMed . 23 March 2022 . 4 April 2022 . 5 April 2022 . https://web.archive.org/web/20220405154323/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fb973a8d-7fea-4a7a-963f-2a8e67a46e55 . live .
  4. Web site: Pluvicto EPAR . European Medicines Agency . 12 October 2022 . 21 December 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. Web site: FDA approves Pluvicto for metastatic castration-resistant prostate can . U.S. Food and Drug Administration . 23 March 2022 . 23 March 2022 . 24 March 2022 . https://web.archive.org/web/20220324031828/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer . live .
  6. Neels OC, Kopka K, Liolios C, Afshar-Oromieh A . Radiolabeled PSMA Inhibitors . Cancers . 13 . 24 . 6255 . December 2021 . 34944875 . 8699044 . 10.3390/cancers13246255 . free .
  7. Web site: Lutetium Lu 177 Vipivotide Tetraxetan (Code C148145) . NCI Thesaurus . 28 February 2022 . 23 March 2022 . 15 April 2022 . https://web.archive.org/web/20220415180304/https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C148145 . live .
  8. Novartis Pluvicto approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer . Novartis . 23 March 2022 . 23 March 2022 . 23 March 2022 . https://web.archive.org/web/20220323205930/https://www.novartis.com/news/media-releases/novartis-pluvictotm-approved-fda-first-targeted-radioligand-therapy-treatment-progressive-psma-positive-metastatic-castration-resistant-prostate-cancer . live .
  9. Web site: Advancing Health Through Innovation: New Drug Therapy Approvals 2022 . U.S. Food and Drug Administration (FDA) . 10 January 2023 . 22 January 2023.
  10. New Drug Therapy Approvals 2022 . U.S. Food and Drug Administration (FDA) . January 2024 . PDF . 14 January 2024 . https://web.archive.org/web/20240114065648/https://www.fda.gov/media/164429/download . 14 January 2024 . live .
  11. US . 11318121 . PSMA binding ligand-linker conjugates and methods for using . Low PS, Kularatne SA . Purdue Research Foundation . 3 May 2022 .
  12. US . 10406240 . PSMA binding ligand-linker conjugates and methods for using . Low PS, Kularatne SA . Purdue Research Foundation . 10 September 2019 .
  13. US . 20160228587 . Labeled inhibitors of prostate specific membrane antigen (psma), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer . 11 August 2016 . Eder M, Kopka K, Schäfer M, Bauder-Wüst U, Haberkorn U, Eisenhut M, Mier W, Benesova M . Deutsches Krebsforschungszentrum DKFZ, Universitaet Heidelberg . Molecular Insight Pharmaceuticals Inc. .
  14. Web site: Endocyte Announces Exclusive License of Phase 3 Ready PSMA-Targeted Radioligand Therapy for Development in Prostate Cancer . 13 April 2022 . www.isotope.com . 29 April 2019 . https://web.archive.org/web/20190429003523/http://www.isotope.com/corporate-overview/news.cfm?nid=Endocyte%20Announces%20Exclusive%20Worldwide%20License%20of%20Phase%203%20Ready%20PSMA%2DTargeted%20Radioligand%20Therapy%20for%20Development%20in%20Prostate%20Cancer . live .
  15. Web site: Taylor PN . 18 October 2018 . Novartis inks $2.1B Endocyte buyout, furthering radiotherapy push . 13 April 2022 . Fierce Biotech . en . 30 November 2020 . https://web.archive.org/web/20201130042908/https://www.fiercebiotech.com/biotech/novartis-inks-2-1b-endocyte-buyout-furthering-radiotherapy-push . live .
  16. Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, Eisenhut M, Kübler W, Holland-Letz T, Giesel FL, Mier W, Kopka K, Haberkorn U . 6 . 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 . November 2015 . 26294298 . 10.2967/jnumed.115.161299 . 23317879 . free .
  17. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, Iravani A, Kong G, Ravi Kumar A, Murphy DG, Eu P, Jackson P, Scalzo M, Williams SG, Sandhu S . 6 . [<sup>177</sup>Lu]-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 . June 2018 . 29752180 . 10.1016/S1470-2045(18)30198-0 . 21674458 .
  18. Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID . 6 . [<sup>177</sup>Lu]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 . February 2021 . 33581798 . 10.1016/s0140-6736(21)00237-3 . 231885243 .
  19. .
  20. Web site: Pluvicto: Pending EC decision . European Medicines Agency (EMA) . 13 October 2022 . 14 October 2022 . 14 October 2022 . https://web.archive.org/web/20221014134736/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/pluvicto . dead . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  21. Web site: Pluvicto Product information . Union Register of medicinal products . 3 March 2023.

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