{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:24:30Z","timestamp":1791102270966,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Most cancers and neoplastic progenitor cells have elevated telomerase activity and preservation of telomeres that promote cellular immortality, making telomerase a rational target for the treatment of cancer. Imetelstat is a first\u2010in\u2010class, 13\u2010mer oligonucleotide that binds with high affinity to the template region of the RNA component of human telomerase and acts as a competitive inhibitor of human telomerase enzymatic activity. Pharmacokinetics, pharmacodynamics, exposure\u2010response analyses, efficacy, and safety of imetelstat have been evaluated in\u00a0vitro, in\u00a0vivo, and clinically in solid tumor and hematologic malignancies, including lower\u2010risk myelodysplastic syndromes (LR\u2010MDS) and myeloproliferative neoplasms. Imetelstat was approved in the United States in June 2024 for the treatment of adult patients with LR\u2010MDS with transfusion\u2010dependent anemia requiring four or more red blood cell units over 8\u2009weeks who have not responded to or have lost response to or are ineligible for erythropoiesis\u2010stimulating agents, with a recommended dosing regimen of 7.1\u2009mg\/kg administered via 2\u2010h intravenous infusion every 4\u2009weeks. In the pivotal trial, significantly more patients treated with imetelstat versus placebo achieved \u22658\u2010week and \u226524\u2010week red blood cell\u2010transfusion independence, and imetelstat was associated with a manageable safety profile characterized primarily by short\u2010lived and manageable neutropenia and thrombocytopenia. This mini\u2010review summarizes the mechanism of action, pharmacokinetic and pharmacodynamic characteristics, clinical development, and clinical efficacy and safety data of imetelstat.<\/jats:p>","DOI":"10.1111\/cts.70076","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T08:40:28Z","timestamp":1731919228000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Imetelstat, a novel, first\u2010in\u2010class telomerase inhibitor: Mechanism of action, clinical, and translational science"],"prefix":"10.1111","volume":"17","author":[{"given":"Ashley L.","family":"Lennox","sequence":"first","affiliation":[{"name":"Geron Corporation  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Huang","sequence":"additional","affiliation":[{"name":"Geron Corporation  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa Kelly","family":"Behrs","sequence":"additional","affiliation":[{"name":"Geron Corporation  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Gonz\u00e1lez\u2010Sales","sequence":"additional","affiliation":[{"name":"Modeling Great Solutions Pharmaceutical Research &amp; Studies, FZE  Dubai UAE"},{"name":"Allucent  Cary North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Bhise","sequence":"additional","affiliation":[{"name":"Allucent  Cary North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wan","sequence":"additional","affiliation":[{"name":"Geron Corporation  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libo","family":"Sun","sequence":"additional","affiliation":[{"name":"Geron Corporation  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tymara","family":"Berry","sequence":"additional","affiliation":[{"name":"Geron Corporation  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faye","family":"Feller","sequence":"additional","affiliation":[{"name":"Geron Corporation  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter N.","family":"Morcos","sequence":"additional","affiliation":[{"name":"Morcos Pharmaceutical Consulting, LLC  Marlboro New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"issue":"12","key":"e_1_2_16_2_1","first-page":"1405","article-title":"Telomeres and cancer","volume":"11","author":"Fan HC","year":"2021","journal-title":"Life (Basel)"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7605428"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5328.955"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb09395.x"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(00)01541-9"},{"issue":"14","key":"e_1_2_16_7_1","first-page":"3931","article-title":"A novel telomerase template antagonist (GRN163) as a potential anticancer agent","volume":"63","author":"Asai A","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208760"},{"key":"e_1_2_16_9_1","volume-title":"RYTELO (imetelstat) [package insert]","year":"2024"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11071923"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM10-3202"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02864"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01895"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000167"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018022012"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222861110"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01724-5"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13160"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250902877680"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2022.0054"},{"key":"e_1_2_16_21_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center.New Drug Application (NDA)\/Biologics Licensing Application (BLA) Multi\u2010disciplinary Review and Evaluation NDA 217779. In: Division of Hematologic Malignancies I OoOD ed.2024."},{"key":"e_1_2_16_22_1","first-page":"2024","article-title":"Clinical pharmacology considerations for the development of oligonucleotide therapeutics","author":"U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER)","year":"2024","journal-title":"Guidance for Industry"},{"key":"e_1_2_16_23_1","volume-title":"Imetelstat NDA 217779, sponsor briefing document, oncologic drugs advisory committee","author":"Geron Corporation","year":"2024"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3204"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2012.04.015"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-138905"},{"key":"e_1_2_16_27_1","unstructured":"United States Food and Drug Administration.Center for Drug Evaluation and Research. Rytelo (imetelstat) NDA217779 approval letter June 6 2024.2024."}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T02:18:28Z","timestamp":1732587508000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":26,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/cts.70076"],"URL":"https:\/\/doi.org\/10.1111\/cts.70076","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70076"}}