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 eight weeks that has not responded to, has lost response to, or is ineligible for erythropoiesis-stimulating agents.

FDA update

Efficacy was evaluated in IMerge (NCT02598661), a randomized (2:1), double-blind, placebo-controlled, multicenter trial in 178 patients with MDS. Patients received an IV infusion of imetelstat 7.1 mg/kg or placebo in 28-day treatment cycles until they experienced disease progression or unacceptable toxicity. Randomization 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 time of 19.5 months (range = 1.4–36.2) in the imetelstat group and 17.5 months (range = 0.7–34.3) in the placebo group based on the proportion of patients who achieved at least 8- and  24-week RBC transfusion independence (RBC-TI), defined as the absence of RBC transfusions during any consecutive 8- or 24-week period, respectively, from randomization 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 < 0.001).

The most common adverse reactions in at least 10% of patients with a difference between arms of more than 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 or myalgia, COVID-19 infections, and headache.

The recommended imetelstat dosage is 7.1 mg/kg administered as an IV infusion over two hours every four weeks. View the full prescribing information for imetelstat here.

The applicant used the Assessment Aid, a voluntary submission to facilitate FDA’s review. Imetelstat was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.