On June 6, 2024, the U.S. Food and Drug Administration (FDA) approved imetelstat (Rytelo), an oligonucleotide telomerase inhibitor, 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, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs).
IMerge Trial
Efficacy was evaluated in IMerge (ClinicalTrials.gov identifier NCT02598661), a randomized, double-blind, placebo-controlled multicenter trial conducted in 178 patients with MDS. Patients were randomly assigned to receive an intravenous infusion of imetelstat at 7.1 mg/kg or placebo in 28-day treatment cycles until disease progression or unacceptable toxicity. Random assignment was stratified by prior red blood cell (RBC) transfusion burden and by International Prognostic Scoring System risk group. All patients received supportive care, which included RBC transfusions.
Efficacy was established after a median follow-up of 19.5 months (range = 1.4–36.2 months) in the imetelstat group and 17.5 months (range = 0.7–34.3 months) in the placebo group based upon the proportion of patients who achieved ≥ 8-week and ≥ 24-week RBC transfusion independence, defined as the absence of RBC transfusion(s) during any consecutive 8-week period, and during any consecutive 24-week period, respectively, from random assignment until the start of subsequent anticancer therapy (if any). The rate of ≥ 8-week RBC transfusion independence was 39.8% (95% confidence interval [CI] = 30.9%–49.3%) in the imetelstat group and 15% (95% CI = 7.1%–26.6%) in the placebo group (P < .001). The rate of ≥ 24-week RBC transfusion independence was 28% (95% CI = 20.1%–37%) in the imetelstat group and 3.3% (95% CI = 0.4%–11.5%) in the placebo group (P < .001).
The most common adverse reactions (≥ 10%, with a difference between arms of > 5% compared with placebo), including laboratory abnormalities, occurring in patients who received imetelstat were decreased platelets, decreased white blood cells, decreased neutrophils, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infection, and headache.
The recommended imetelstat dosage is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This product was granted Orphan Drug designation.
