Imetelstat (Rytelo)

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Mechanism of action

From NCI Drug Dictionary: The sodium salt of imetelstat, a synthetic lipid-conjugated, 13-mer oligonucleotide N3' P5'-thio-phosphoramidate with potential antineoplastic activity. Complementary to the template region of telomerase RNA (hTR), imetelstat acts as a competitive enzyme inhibitor that binds and blocks the active site of the enzyme (a "telomerase template antagonist"), a mechanism of action which differs from that for the antisense oligonucleotide-mediated inhibition of telomerase activity through telomerase mRNA binding. Inhibition of telomerase activity in tumor cells by imetelstat results in telomere shortening, which leads to cell cycle arrest or apoptosis. Link to company website

Preliminary data

Essential thrombocythemia

  1. CP14B015: Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Röth A, Daskalakis M, Burington B, Stuart M, Snyder DS. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med. 2015 Sep 3;373(10):920-8. link to original article PubMed NCT01243073

Myelodysplastic syndrome

  1. IMerge: Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jan 20;403(10423):249-260. Epub 2023 Dec 1. Erratum in: Lancet. 2024 Jan 20;403(10423):248. link to original article PubMed NCT02598661


  1. CR107110: Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, Wassie E, Schimek L, Hanson CA, Gangat N, Wang X, Pardanani A. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3;373(10):908-19. link to original article PubMed NCT01731951

History of changes in FDA indication

  • 2024-06-06: Approved for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). (Based on IMerge)

Also known as

  • Code name: GRN-163L
  • Brand name: Rytelo