Imetelstat for Transfusion-Dependent
Anemia in MDS | Image credit:
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The European Commission (EC) has granted marketing authorization for imetelstat (Rytelo) as a monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low-, low-, or intermediate-risk myelodysplastic syndrome (MDS) who not harbor an isolated deletion 5q cytogenetic abnormality and experienced an unsatisfactory response to or are ineligible for erythropoietin-based therapy (ESAs).1
This regulatory decision makes imetelstat the first and only telomerase inhibitor approved by the EC. The marketing authorization applies to all 27 member states of the European Union, Iceland, Norway, and Liechtenstein.
Results from the phase 3 IMerge trial (NCT02598661) supported this marketing authorization. Prior data published in The Lancet showed that, at a median follow-up of 19.5 months (IQR, 12.0-23.4) in the imetelstat arm (n = 118) and 17.5 months (IQR, 12.1-22.7) in the placebo arm (n = 60), red blood cell transfusion independence (RBC-TI) for at least 8 consecutive weeks was achieved by 40% (95% CI, 30.9%-49.3%) vs 15% (95% CI, 7.1%-26.6%) of patients, respectively (P = .0008).2 Additionally, the rate of RBC-TI at 24 weeks or greater was 28% (95% CI, 20.1%-37%) in the imetelstat arm vs 3.3% (95% CI, 0.4%-11.55%) in the placebo arm (P < .001).3
“I am thrilled that the EC has approved imetelstat in lower-risk MDS. The long-term and durable responses observed in the phase 3 IMerge study reinforce the practice-changing potential of telomerase inhibition as a clinically meaningful and differentiated option for the treatment of lower-risk MDS,” Uwe Platzbecker, MD, chief medical officer at the University Hospital Carl Gustav Carus Dresden in Germany, and the co-lead author of data from IMerge published in The Lancet, stated in a news release.1 “Physicians and patients in Europe are now one step closer to accessing a novel treatment that, in addition to having a generally manageable safety profile, has the potential to provide extended and continuous RBC-TI.”
Notably, data from IMerge also supported the June 2024 FDA approval of imetelstatfor adult patients with low- to intermediate-1–risk MDS and transfusion-dependent anemia requiring 4 or more RBC units over 8 weeks who have not responded to or have lost response to or are not eligible for ESAs.3
“As the first and only treatment of its kind, imetelstat represents an important new option – significantly reducing the need for RBC transfusions for people living with lower-risk MDS who are battling debilitating symptoms like anemia and fatigue,” Joseph Eid, MD, the executive vice president of Research and Development at Geron, added in the news release.1 “This approval from the EC, just 9 months following approval in the United States, underscores the positive benefit for these patients demonstrated in our clinical trials and we look forward to making this innovative therapy accessible to eligible patients in Europe."
IMerge was a double-blind, placebo-controlled study that enrolled adult patients with low- or intermediate-1–risk MDS according to the International Prognostic Scoring System (IPSS).2 Patients were RBC transfusion dependent, defined as requiring at least 4 units of RBCs over an 8-week period and had disease that was either relapsed/refractory to ESAs or were ineligible for ESA therapy.
Eligible patients were randomly assigned 2:1 to receive intravenous imetelstat at a starting dose of 7.5 mg/kg every 4 weeks or placebo. The study’s primary end point was the 8-week RBC-TI rate. Key secondary end points included the 24-week RBC-TI rate, the duration of RBC-TI, and hematologic response rate.
Imetelstat's safety profile has been well-characterized, with notable adverse effects (AEs) including thrombocytopenia and neutropenia.1 These AEs are generally transient and manageable. The most commonly reported grade 3 or higher AEs were neutropenia (69%) and thrombocytopenia (63%), which lasted a median duration of less than 2 weeks. More than 80% of these cases resolved to less than grade 2 within 4 weeks.
References
Geron announces European Commission approval of RYTELO® (imetelstat), a first-in-class telomerase inhibitor, for the treatment of adults with transfusion-dependent anemia due to lower-risk MDS. News release. Geron. March 11, 2025. Accessed March 12, 2025. https://ir.geron.com/investors/press-releases/press-release-details/2025/Geron-Announces-European-Commission-Approval-of-RYTELO-imetelstat-a-First-in-Class-Telomerase-Inhibitor-for-the-Treatment-of-Adults-With-Transfusion-Dependent-Anemia-Due-to-Lower-Risk-MDS/default.aspx
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. Lancet. 2024;403(10423):249-260. doi:10.1016/S0140-6736(23)01724-5
FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia. FDA. June 6, 2024. Accessed March 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imetelstat-low-intermediate-1-risk-myelodysplastic-syndromes-transfusion-dependent