On June 6, 2024, the Food and Drug Administration (FDA) approved imetelstat (Rytelo, Geron Corporation), an oligonucleotide telomerase inhibitor, for the treatment of adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) who have transfusion-dependent anemia. This approval is specifically for patients requiring four or more red blood cell (RBC) units over eight weeks and who have not responded to, lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs).

Clinical Trial and Efficacy

The efficacy of imetelstat was evaluated in the IMerge trial (NCT02598661), a randomized, double-blind, placebo-controlled multicenter study involving 178 MDS patients. Participants received either an intravenous infusion of imetelstat at 7.1 mg/kg or a placebo in 28-day treatment cycles until disease progression or unacceptable toxicity occurred. The trial stratified patients based on their prior RBC transfusion burden and International Prognostic Scoring System (IPSS) risk group. All patients received supportive care, including RBC transfusions.

After a median follow-up period of 19.5 months for the imetelstat group and 17.5 months for the placebo group, efficacy was assessed. The primary endpoint was the proportion of patients achieving RBC transfusion independence (RBC-TI) for periods of ≥ 8 weeks and ≥ 24 weeks. In the imetelstat group, 39.8% (95% CI: 30.9, 49.3) achieved ≥ 8-week RBC-TI, compared to 15% (95% CI: 7.1, 26.6) in the placebo group (p-value < 0.001). Additionally, 28% (95% CI: 20.1, 37) of the imetelstat group achieved ≥ 24-week RBC-TI, compared to 3.3% (95% CI: 0.4, 11.5) in the placebo group (p-value < 0.001).

Adverse Reactions

The most common adverse reactions associated with imetelstat, occurring in ≥ 10% of patients and with a difference of > 5% compared to placebo, included 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.

Recommended Dosage

The recommended dosage for imetelstat is 7.1 mg/kg administered as an intravenous infusion over two hours every four weeks. This product has been granted orphan drug designation.

Highlights

• FDA approved imetelstat for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) and transfusion-dependent anemia.
• Approval based on IMerge trial results showing significant RBC transfusion independence.
• 39.8% of imetelstat group achieved ≥ 8-week RBC transfusion independence vs. 15% in placebo group.
• 28% of imetelstat group achieved ≥ 24-week RBC transfusion independence vs. 3.3% in placebo group.
• Common adverse reactions include decreased platelets and white blood cells, increased liver enzymes, fatigue, and prolonged partial thromboplastin time.
• Recommended dosage is 7.1 mg/kg via intravenous infusion every four weeks.