FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia

Regulatory approval: On June 6, 2024, the FDA approved imetelstat (Rytelo; Geron) for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) and transfusion-dependent anemia (≥4 RBC units over 8 weeks) who have not responded to, lost response to, or are ineligible for erythropoiesis-stimulating agents. Approval was supported by the IMerge randomized, double-blind, placebo-controlled trial showing higher ≥8-week and ≥24-week RBC transfusion independence rates versus placebo.

FDA approval (June 6, 2024)

The US Food and Drug Administration (FDA) approved imetelstat (Rytelo; Geron Corporation), an oligonucleotide telomerase inhibitor, for adults with low- to intermediate-1 risk MDS with transfusion-dependent anemia requiring ≥4 red blood cell (RBC) units over 8 weeks who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs).

Supporting evidence: IMerge (NCT02598661)

Efficacy was evaluated in IMerge, a randomized (2:1), double-blind, placebo-controlled, multicenter trial in 178 patients with MDS. Patients received imetelstat 7.1 mg/kg IV or placebo in 28-day cycles until progression or unacceptable toxicity, with randomization stratified by prior RBC transfusion burden and IPSS risk group. Supportive care included RBC transfusions.

After median follow-up of 19.5 months (imetelstat) vs 17.5 months (placebo), efficacy was based on RBC transfusion independence (RBC-TI):

  • ≥8-week RBC-TI: 39.8% (95% CI 30.9–49.3) vs 15% (95% CI 7.1–26.6); p < 0.001
  • ≥24-week RBC-TI: 28% (95% CI 20.1–37) vs 3.3% (95% CI 0.4–11.5); p < 0.001

Safety and dosing

Common adverse reactions (≥10% and >5% difference vs placebo) included decreased platelets/WBC/neutrophils, elevated AST/ALP/ALT, fatigue, prolonged PTT, arthralgia/myalgia, COVID-19 infections, and headache.

Recommended dosage: 7.1 mg/kg IV infusion over 2 hours every 4 weeks. The product received orphan drug designation.

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