High-Cost Therapy Profile: June 2024

June 14, 2024

Detailed information about Imetelstat Intravenous (IV)

High-Cost Therapy Profile


Imetelstat Intravenous (IV)


Proposed indications

For the treatment of transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks in adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) who have failed to respond, or have lost response to, or are ineligible for erythropoiesis stimulating agents (ESA).

U.S. Food and Drug Administration (FDA) approval timeline

Approved June 6, 2024

  • Fast Track
  • Orphan Drug

Place in therapy

Imetelstat (Rytelo™) is a telomerase inhibitor. It selectively targets malignant hematopoietic stem and progenitor cells with high telomerase activity by directly binding to the RNA template, resulting in malignant cell apoptosis and potential disease-modifying activity. This mechanism allows for the recovery of non-malignant bone marrow and blood cell production.

  • Imetelstat is a first-in-class telomerase inhibitor and provides a new mechanism of action leading to transfusion independence when treating MDS-related anemia after treatment with ESAs has failed or in patients who are ESA ineligible.
  • Imetelstat is being studied in patients with low or intermediate-1 risk myelodysplastic syndromes with ESA-relapsed, ESA-refractory, or ESA ineligible disease.
  • In the clinical trial, imetelstat 7.5 mg/kg was administered IV over 2 hours every 4 weeks until disease progression or unacceptable toxicity occurred. However, per the FDA approval, the recommended dose of imetelstat is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks.
  • Treatment with imetelstat in the clinical trial for LR-MDS resulted in statistically significant improvements in RBC-transfusion independence (TI) as compared to placebo.
  • Overall survival and disease progression, including progression to acute myeloid leukemia, are being evaluated in the ongoing extension phase. A sub study on ventricular repolarization is also ongoing.
  • Imetelstat may compete with Reblozyl® (luspatercept-aamt) in patients with ring sideroblastic MDS.
  • This product is also being studied in relapsed/refractory myelofibrosis, frontline myelofibrosis (combination therapy), acute myeloid leukemia or high-risk MDS who are relapsed, refractory, or intolerant to hypomethylating agents, and relapsed/refractory acute myeloid leukemia (combination therapy; planned trial).

Understanding your data

Imetelstat is an intravenous temolerase inhibitor. Telomerase is an enzyme that supports telomere structure and enables continued proliferation of malignant cells. This enzyme is upregulated in malignant stem and protigenitor cells which leads to the ongoing proliferation of malignant cells. Inhibition of this enzyme with imetelstat allows for selective targeting of malignant stem and progenitor cells in the bone marrow. The following are clinical trials evaluating imetelstat in MDS:

  • NCT02598661: Phase 2/3 Trial Evaluating Imetelstat (GRN163L) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
  • NCT05583552 IMpress: A Phase II Study Evaluating the Efficacy and Safety of Imetelstat in Patients With HR Myelodysplastic Syndromes or AML Failing HMA-based Therapy

Identification of patients would reflect the clinical trials criteria listed in the studies above, as well as diagnosis codes identified from claims data requiring among others:

Common measurable inclusion criteria:

  • Age ≥ 18 years
  • Diagnosis of myelodysplastic syndrome or myeloproliferative neoplasm with ring sideroblasts and thrombocytosis
  • Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks

Common measurable exclusion criteria:

  • Prior treatment with hypomethylating agent (azacitidine, decitabine) or lenalidomide




Myelodysplastic syndrome or myeloproliferative neoplasm with ring sideroblasts and thrombocytosis ICD-10: D46x
Transfusions HCPCS: 36430, P9010, P9011, P9012, P9016, P9017, P9021, P9022, P9023, P9038, P9039, P9040, P9043, P9044, P9048, P9051, P9054, P9056, P9057, P9058, P9059, P9060



30233K1, 30233L1, 30233M1, 30233N1, 30233P1

Azacitidine, decitabine or lenalidomide GPI10: 2130000300, 2130001500,  9939405000


HCPCS: J9025, J0893, J0894

Clinical deep dive

Disease state overview

Myelodysplastic syndromes (MDS) are classified as disorders in which there are abnormal (dysplastic) hematopoietic stem cells in the bone marrow, leading to problems forming healthy, new blood cells (i.e., leukocytes, red blood cells, platelets). The defective cells that are formed tend to die earlier than a normal cell would, leading to a deficiency of blood cells. Without a normal number of blood cells, patients may experience infection, bleeding or bruising, and/or anemia. MDS is considered a hematologic neoplasm; it can be idiopathic, or it can be caused by exposure to certain environmental chemicals such as radiation or prior exposure to chemotherapy. Idiopathic MDS is typically seen in the elderly population. In approximately 30% of patients, MDS can progress into Acute Myeloid Leukemia (AML).

The revised International Prognostic Scoring System (IPSS-R) is a risk stratification too used by providers to aid in treatment decisions for patients with MDS. Approximately 70% of patients with MDS are classified as very low, low, or intermediate risk as per the IPSS-R. Many patients with low-risk MDS are red blood cell transfusion-dependent (RBC-TD), leading to increased mortality and poor quality of life. Goals of treament include eliminating the need for transfusions, increasing hemoglobin concentrations, and increasing survival rates and quality of life.  The IPSS-R very low risk group has a median survival rate of 8.8 years, whereas, the very high risk group has a median survival of 0.8 years.


Typically, MDS occurs and is diagnosed in patients 65 and older. It has been estimated through the Surveillance Epidemiology and End Results (SEER)-Medicare database from 2007-2011 that the incidence of MDS is approximately 4.9 per 100,000 persons with approximately 20,541 new cases developing annually. Most commonly MDS is found in patients over the age of 80, with an incidence of 58 per 100,000. The prevalence of MDS is not well reported, but it is estimated to be between 60,000 and 170,000 patients in the United States.


Allogenic stem cell transplant is the only available curative treatment for MDS; however, this procedure is challenging for elderly patients who are more commonly diagnosed with this condition. Select intermediate-risk and high risk patients can be candidates for allogenic stem cell transplant or systemic therapy. Erythropoiesis stimulating agents (ESAs) are standard of care for symptomatic anemia in patients with lower-risk MDS (LR-MDS); though, most patients are refractory to ESAs or relapse within approximately two years. Patients with serum erythropoietin levels of more than 500 mU/mL will likely not experience improvement in anemia with ESA therapy and, therefore, do not qualify for treatment with ESAs. Hypomethylating agents (e.g., azacitadine, decitabine) and lenalidomide are also used to treat MDS. Low-risk patients are typically managed with supportive care (e.g., RBC and platelet transfusions, hematopoietic growth factors such as epoetin alfa and darbepoetin alfa, granulocyte colony stimulating factors [G-CSFs], and iron chelation therapy), but they also can be treated with systemic agents. Later line treatment options for anemia with MDS are limited to select populations. Luspatercept-aamt (Reblozyl) can be used in patients with MDS with ring sideroblasts, and lenalidomide is used in patients with MDS associated with a 5q deletion. Because many patients become refractory, ineligible, or relapse with ESAs and later line therapies are only indicated in select patient populations, there is a need for more robust treatment options that target the underlying dysplastic cells.

Drug and clinical trial overview

The randomized, double-blind, placebo-controlled, phase 3 IMerge trial (NCT02598661) evaluated imetelstat in 178 adults with RBC transfusion-dependent, low- or intermediate-risk MDS that was relapsed, refractory to, or ineligible for ESA therapy. Patients had not received prior treatment with azacitidine, decitabine, or lenalidomide. The median follow-up was 19.5 months in the imetelstat group and 17.5 months in the placebo group. The study demonstrated that significantly more patients treated with imetelstat achieved the primary endpoint of RBC transfusion independence in ≥ 8 weeks compared to those who were given placebo (40% versus 15%, respectively; p=0.0008). In addition, 28% and 18% of patients treated with imetelstat remained RBC transfusion-independent at ≥ 24 weeks and ≥ 1 year, respectively, compared to 3% and 2%, respectively, in those who received placebo. Grade 3 to 4 treatment-emergent adverse events (TEAEs) occurred in 91% of patients in the imetelstat group compared to 47% in the placebo group. Of these, neutropenia and thrombocytopenia were the most common, and occurred most often during the first three treatment cycles. Cytopenia was managed with treatment delays and dose adjustments in accordance with the study protocol.

Pipeline (late-stage development)







Canakinumab Novartis SC Interleukin 1 (IL-1) antagonist MDS Phase 2
Rigosertib Onconova PO/IV Polo-like kinase (PLK) inhibitor MDS Phase 3
Venetoclax AbbVie PO BCL-2 inhibitor MDS Phase 3
Eprenetapopt Aprea Therapeutics IV P53 reactivator MDS Phase 3
Tamibarotene Syros Pharmaceuticals PO Retinoic acid receptor alpha agonist MDS Phase 3
Pevonedistat Takeda IV Nedd8-activating enzyme inhibitor MDS Phase 3
Gilteritinib Fumarate Astellas PO Receptor tyrosine kinase inhibitor MDS Phase 3
  1. Errata to FDA Briefing Document: March 14, 2024 Oncologic Drugs Advisory Committee. Food and Drug Administration. March 14, 2024. Accessed May 2, 2024. https://www.fda.gov/media/176967/download.
  2. FDA Briefing Document: March 14, 2024 Oncologic Drugs Advisory Committee. Food & Drug Administration. March 14, 2024. Accessed May 2, 2024. https://www.fda.gov/media/176966/download.
  3. Center for Drug Evaluation and Research. FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia. U.S. Food and Drug Administration. June 6, 2024. Accessed June 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imetelstat-low-intermediate-1-risk-myelodysplastic-syndromes-transfusion-dependent.
  4. Imetelstat: A first-in-class investigational telomerase inhibitor. Geron. March 6, 2024. Accessed May 2, 2024. https://www.geron.com/research-and-development/imetelstat/#:~:text=Imetelstat%2C%20our%20novel%20investigational%20telomerase%20inhibitor%2C%20binds%20to,such%20as%20myelodysplastic%20syndromes%20%28MDS%29%20and%20myelofibrosis%20%28MF%29.
  5. Platzbecker U, Santini V, Fenaux P, et al. 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. The Lancet. 2024;403(10423):249-260. doi:10.1016/s0140-6736(23)01724-5
  6. Clinical trials exploring IMETELSTAT. Geron. February 29, 2024. Accessed May 13, 2024. https://www.geron.com/research-and-development/clinical-trials/.
  7. What are myelodysplastic syndromes? American Cancer Society. Accessed May 3, 2024. https://www.cancer.org/cancer/types/myelodysplastic-syndrome/about/what-is-mds.html.
  8. Dotson JL, Lebowicz Y. Myelodysplastic syndrome. StatPearls [Internet]. July 18, 2022. Accessed May 3, 2024. https://www.ncbi.nlm.nih.gov/books/NBK534126/.
  9. Myelodysplastic syndrome (MDS) research funded by LLS. Myelodysplastic Syndrome (MDS) Research Funded by LLS | Leukemia and Lymphoma Society. Accessed May 13, 2024. https://www.lls.org/research/myelodysplastic-syndrome-mds-research-funded-lls.
  10. Reblozyl [prescribing information]. Summit, NJ Bristol Myers Squibb; August 2023.
  11. Revlimid [prescribing information]. Princeton, NJ Bristol Myers Squibb; March 2023.
  12. Survival rates for myelodysplastic syndromes: MDS Prognosis. Survival Rates for Myelodysplastic Syndromes | MDS Prognosis | American Cancer Society. Accessed May 3, 2024. https://www.cancer.org/cancer/types/myelodysplastic-syndrome/detection-diagnosis-staging/survival.html.
  13. Steensma DP, Fenaux P, Van Eygen K, et al. Imetelstat Achieves Meaningful and Durable Transfusion Independence in High Transfusion-Burden Patients With Lower-Risk Myelodysplastic Syndromes in a Phase II Study. J Clin Oncol. 2021 Jan 1;39(1):48-56. doi: 10.1200/JCO.20.01895. Epub 2020 Oct 27. PMID: 33108243..
  14. Geron Corp. A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment. Available from: https://clinicaltrials.gov/study/NCT02598661. Accessed April 11, 2024.
  15. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Myelodysplastic Syndromes. Version 1.2023. National Comprehensive Cancer Network, 2023. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed April 2024.
  16. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Myelodysplastic Syndromes. Version 1.2023. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed May 2024.
  17. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/. Accessed May 13, 2024.
  18. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/. Accessed May 15, 2024.
  19. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/. Accessed May 15, 2024.
  20. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/. Accessed May 15, 2024.

The information provided has been developed based on available information as of June 10, 2024. This therapy is FDA approved, and content may change as more information becomes available. Caution should be used when developing formulary and utilization management strategies. The trademarked drug name is the property of its respective manufacturer.

By receipt of this report, each recipient agrees that the information contained herein will be kept confidential and that the information will not be photocopied, reproduced or distributed to or disclosed to others at any time without the prior written consent of Magellan Rx Management, a Prime Therapeutics company. The information contained in this report is intended for educational purposes only and is not intended to define a standard of care or exclusive course of treatment, nor be a substitute for treatment.

Drug names are the property of their respective owners.

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