FDA Grants Approval to Imetelstat for Patients With Low to Intermediate-1 Risk Myelodysplastic Syndrome With Transfusion-Dependent Anemia

On June 6, 2023, the Food and Drug Administration (FDA) granted approval to imetelstat, an oligonucleotide telomerase inhibitor, for patients with low to intermediate-1 risk myelodysplastic syndrome (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell unit transfusion over 8 weeks, who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs).

Imelstat efficacy was analyzed by investors through the IMerge trial, a 2 to 1 randomized, double-blind, placebo-controlled multicenter trial. The trial included 178 patients with MDS, who received an intravenous infusion of imetelstat at 7.1 mg/kg or a placebo in 28-day treatment cycles until disease progression or unacceptable toxicity. Randomization was stratified by prior red blood cell (RBC) transfusion burden and by International Prognostic Scoring System (IPSS) risk group. All patients included in the trial received supportive care, which included RBC transfusions.

In this study, efficacy was established after a median follow up time of 19.5 months in the imetelstat group and 17.5 months 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 transfusions during any consecutive 8 week period, and during any consecutive 24 week period, respectively, from randomization until the start of any subsequent anti-cancer therapy. The rate of ≥ 8-week RBC-TI was found to be 39.8% (95% confidence interval [CI], 30.9 to 49.3) in the imetelstat group and 15% (95% CI, 7.1 to 26.6) in the placebo group (p-value < 0.001). The rate of ≥ 24-week RBC-TI was 28% (95% CI, 20.1 to 37) was found to be in the imetelstat group and 3.3% (95% CI, 0.4 to 11.5) in the placebo group (p-value < 0.001).

As far as safety, investigators documented that the most common adverse reactions, 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. 

Source:

FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia. Press Release. The US Food and Drug Administration. Published online June 6, 2023. Accessed June 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imetelstat-low-intermediate-1-risk-myelodysplastic-syndromes-transfusion-dependent