Imetelstat

12.1. Mechanism of Action Imetelstat is an oligonucleotide human telomerase inhibitor that binds to the template region of the RNA component of human telomerase (hTR), inhibits telomerase enzymatic activity and prevents telomere binding.

• 1. INDICATIONS AND USAGE RYTELO is indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 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 (ESA).ICD-10: D64.9

• 4. CONTRAINDICATIONS None.contraindicated

2. DOSAGE AND ADMINISTRATION The recommended dosage of RYTELO is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks. ( 2.1 ) Premedicate prior to dosing with RYTELO for potential infusion-related reactions. ( 2.2 ) See full prescribing information for preparation and administration instructions. ( 2.4 ) 2.1. Recommended Dosage The recommended dosage of RYTELO is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks. Discontinue RYTELO if a patient does not experience a decrease in red blood cell (RBC) transfusion burden after 24 weeks of treatment (administration of 6 doses) or if unacceptable toxicity occurs at any time [see Dosage and Administration (2.3) ] . 2.2. Recommended Premedications Administer the following pre-treatment medications at least 30 minutes prior to dosing to prevent or reduce potential infusion-related reactions: diphenhydramine (or equivalent) 25 mg to 50 mg, intravenously or orally hydrocortisone (or equivalent) 100 mg to 200 mg, intravenously or orally Monitor patients for adverse reactions for at least one hour after the infusion has been completed [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ] . 2.3. Dosage Modifications for Adverse Reactions Recommended dose reductions for Grade 3 and Grade 4 adverse reactions are found in Table 1. The management of Grade 3 and Grade 4 adverse reactions may require temporary dose delay, dose reduction, or treatment discontinuation and are presented in Table 2 and Table 3.

5. WARNINGS AND PRECAUTIONS Thrombocytopenia : Grade 3 and Grade 4 thrombocytopenia occurred; obtain complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as recommended. ( 2.3 , 5.1 ) Neutropenia : Grade 3 and Grade 4 neutropenia occurred; obtain complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as recommended. ( 2.3 , 5.2 ) Infusion-Related Reactions : Premedicate before infusion. Interrupt, decrease the rate of infusion, or permanently discontinue RYTELO based on severity. ( 2.2 , 2.3 , 5.3 ) Embryo-Fetal Toxicity : Can cause embryo-fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1. Thrombocytopenia RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO [see Adverse Reactions (6.1) ] . Median time to onset of first occurrence of Grade 3 or 4 decreased platelets was 6 weeks (range: 2 to 88 weeks) and median time to recovery from each occurrence of Grade 3 or 4 decreased platelets to Grade 2 or lower, or last value available, was 1.3 weeks (range: 0.1 to 13 weeks).

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Thrombocytopenia [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities are decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Geron Corporation at 1-855-437-6664 (1-855-GERONMI) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Low- to Intermediate-Risk Myelodysplastic Syndromes The safety of RYTELO was evaluated in a randomized, double-blind, placebo-controlled, multicenter trial (IMerge) in 177 adult patients with International Prognostic Scoring System (IPSS) low- to intermediate-1 risk MDS who were transfusion-dependent and relapsed or refractory to or ineligible for ESA treatment [see Clinical Studies (14) ] .

8. USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1. Pregnancy Risk Summary Based on findings in animal studies, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on RYTELO use in pregnant women to evaluate for drug-associated risk. In embryo-fetal developmental toxicity studies, administration of imetelstat to pregnant mice and rabbits during the period of organogenesis resulted in embryo-fetal mortality, which in mice occurred at maternal exposures approximately 2.5 times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus [see Data ] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal developmental toxicity studies, imetelstat was administered by IV bolus injection at doses of 4.7, 9.4, 14.1 or 28.2 mg/kg/day on gestation days 6, 9, and 12 in mice, or by 2-hour intravenous infusion at doses of 4.7, 14.1, or 28.2 mg/kg on gestation days 6 and 13 in rabbits. In rabbits, the dose of 28.2 mg/kg was maternally toxic.

Metabolism

12.3. Pharmacokinetics Imetelstat plasma geometric mean (coefficient of variation [CV] %) maximum concentration (C max ) is 18.3 µM (27.3%) and the area under the concentration-time curve from time 0 to 28 days (AUC 0-28 ) was 114.2 h*µM (43.2%).

• Jun 6, 2024NDANDA217779Geron

1. 1Platelet Count Decreased2616%
2. 2Thrombocytopenia2415%
3. 3Haemoglobin Decreased2314%
4. 4Cytopenia2012%
5. 5Neutropenia1710%
6. 6Infusion Related Reaction95.6%
7. 7Neutrophil Count Decreased84.9%
8. 8White Blood Cell Count Decreased84.9%
9. 9Dyspnoea74.3%
10. 10Death63.7%
11. 11Drug Ineffective63.7%
12. 12Pancytopenia63.7%
13. 13Fatigue53.1%
14. 14Intercepted Product Preparation Error53.1%
15. 15Cardiac Failure Congestive42.5%

The 10 most recently updated of 46 ClinicalTrials.gov registrations naming Imetelstat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study to Evaluate Imetelstat in Patients With High-Risk MDS or AML Failing HMA-based Therapy
  Active not recruiting · Phase 2 · Interventional · 46 enrolled · GCP-Service International West GmbH
  NCT05583552updated 2026-05-12
• Phase 2 Study Of Imetelstat for Patient With Myelodysplastic/Myeloproliferative Neoplasms
  Not yet recruiting · Phase 2 · Interventional · 30 enrolled · M.D. Anderson Cancer Center
  NCT07549451updated 2026-04-24
• Imetelstat Combinations in Relapsed AML
  Recruiting · Phase 1 · Interventional · 36 enrolled · Douglas Tremblay
  NCT07320235updated 2026-04-22
• A Study to Find the Highest Dose of Imetelstat in Combination With Fludarabine and Cytarabine for Patients With AML, MDS or JMML That Has Come Back or Does Not Respond to Therapy
  Recruiting · Phase 1 · Interventional · 36 enrolled · Children's Oncology Group
  NCT06247787updated 2026-04-20
• A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Participants With Myelofibrosis
  Recruiting · Phase 1 · Interventional · 36 enrolled · Geron Corporation
  NCT05371964updated 2026-01-06
• Study to Evaluate Imetelstat (GRN163L) in Participants With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 289 enrolled · Geron Corporation
  NCT02598661updated 2026-01-05
• A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment
  Active not recruiting · Phase 3 · Interventional · 327 enrolled · Geron Corporation
  NCT04576156updated 2025-12-04
• Investigational Drug in Combination With Two Chemotherapy Drugs in Women With Locally Recurrent or Metastatic Breast Cancer
  Withdrawn · Phase 1 · Phase 2 · Interventional · 0 enrolled · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
  NCT01349088updated 2025-05-02
• Expanded Access for Treatment With Imetelstat
  Approved for marketing · Expanded access · Geron Corporation
  NCT05937568updated 2024-06-24
• AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors
  Completed · Phase 2 · Interventional · 46 enrolled · Eastern Cooperative Oncology Group
  NCT00427349updated 2023-07-05

Frequently asked questions

How does Imetelstat work?

12.1. Mechanism of Action Imetelstat is an oligonucleotide human telomerase inhibitor that binds to the template region of the RNA component of human telomerase (hTR), inhibits telomerase enzymatic activity and prevents telomere binding.

What is Imetelstat used for?

According to FDA labeling, Imetelstat carries indications including: 1. INDICATIONS AND USAGE RYTELO is indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 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 (ESA).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Imetelstat?

Imetelstat is classified as Other antineoplastic agents, Oligonucleotide Telomerase Inhibitor, Enzyme Inhibitors, Oligonucleotide Telomerase Inhibitors.

What are the brand names for Imetelstat?

Imetelstat is marketed under brand names including Rytelo.

What are the contraindications for Imetelstat?

Imetelstat labeling lists contraindications including: 4. CONTRAINDICATIONS None.. Always consult the full prescribing information and a clinician.