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| Trade names | Rytelo |
| Other names | GRN163L |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a624035 |
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| Routes of administration | Intravenous |
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| Formula | C148H211N68O53P13S13 |
| Molar mass | 4610.18 g·mol−1 |
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Imetelstat, sold under the brand nameRytelo, is ananti-cancer medication used for the treatment ofmyelodysplastic syndromes withtransfusion-dependent anemia.[1] Imetelstat is anoligonucleotide telomerase inhibitor.[1][2][3] By blocking telomerase activity, imetelstat causes telomere shortening, inhibits the proliferation of malignant stem and progenitor cells and induces cell death, ultimately leading to a reduction in malignant clones.[2]
The most common adverse reactions include decreased platelets, decreased white blood cells, decreased neutrophils, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.[4]
Imetelstat was approved for medical use in the United States in June 2024.[4][5][6] The USFood and Drug Administration (FDA) considers it to be afirst-in-class medication.[7]
Imetelstat isindicated for the treatment of adults with low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents.[1][4]
Imetelstat is the firsttelomeraseinhibitor to enterclinical trials.[8]
Chemically, imetelstat is a syntheticconjugate consisting of three parts: GRN163, athiophosphoramideoligonucleotide, and apalmitoyl lipid group.[8] GRN163 is the pharmacological component with telomerase inhibition based on experiments with poly-G oligonucleotides first conducted at the University of Nebraska Medical Center under contract with Lynx Therapeutics.[9] The palmitic acid moiety is conjugated via aphosphothioate linkage to the backbone of the antisense oligonucleotide.[medical citation needed] Telomere shortening and lower cell viability are observed after inhibition of telomerase activity in vitro.[medical citation needed] IC50 values ranged from 50 to 200nM for 10 different pancreatic cell lines.[10]
The efficacy of imetelstat was evaluated in IMerge (NCT02598661), a randomized (2:1), double-blind, placebo-controlled multicenter trial in 178 participants with myelodysplastic syndromes.[4] Participants received an intravenous infusion of imetelstat 7.1 mg/kg or placebo in 28-day treatment cycles until disease progression or unacceptable toxicity.[4] Randomization was stratified by prior red blood cell transfusion burden and by International Prognostic Scoring System (IPSS) risk group.[4] All participants received supportive care, which included red blood cell transfusions.[4]
Imetelstat was approved for medical use in the United States in June 2024.[4] The FDA granted the application for imetelstatorphan drug designation.[4][11][12]
In December 2024, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Rytelo, intended for the treatment of adults with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes.[2] The applicant for this medicinal product is Geron Netherlands B.V.[2] Imetelstat was authorized for medical use in the European Union in March 2025.[2]
Imetelstat is theinternational nonproprietary name.[13]
This article incorporates text from this source, which is in thepublic domain.