On June 6, 2024, the Food and Drug Administration approved imetelstat, 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 or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs).

Efficacy was evaluated in IMerge (NCT02598661), a randomised (2:1), double-blind, placebo-controlled multicenter trial in 178 patients with MDS.

Patients received an intravenous infusion of imetelstat 7.1 mg/kg or placebo in 28-day treatment cycles until disease progression or unacceptable toxicity.

Randomisation was stratified by prior red blood cell (RBC) transfusion burden and by International Prognostic Scoring System (IPSS) risk group.

All patients received supportive care, which included RBC transfusions.

Efficacy was established after a median follow up time of 19.5 months (range: 1.4 to 36.2) in the imetelstat group and 17.5 months (range: 0.7 to 34.3) in the placebo group based upon the proportion of patients who achieved ≥ 8-week and ≥ 24-week RBC transfusion independence (RBC-TI), defined as the absence of RBC transfusion(s) during any consecutive 8 week period, and during any consecutive 24 week period, respectively, from randomisation until the start of subsequent anti-cancer therapy (if any).

The rate of ≥ 8-week RBC-TI was 39.8% (95% CI: 30.9, 49.3) in the imetelstat group and 15% (95% CI: 7.1, 26.6) in the placebo group (p-value < 0.001).

The rate of ≥ 24-week RBC-TI 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-value < 0.001).

The most common adverse reactions (≥ 10% with a difference between arms of > 5% compared to placebo), including laboratory abnormalities, 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 infections, and headache.

The recommended imetelstat dosage is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks.

Source: FDA