US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia
Abstract
On June 6, 2024, the US Food and Drug Administration (FDA) approved imetelstat (RYTELO, Geron) for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring ≥4 red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents. The approval was based on a randomized (2:1), double-blind, placebo-controlled multicenter trial, Study MDS3001. In the protocol-specified primary analysis, the ≥8-week RBC transfusion independence (RBC-TI) rate was 39.8% (95% CI, 30.9 to 49.3) in the imetelstat group versus 15% (95% CI, 7.1 to 26.6) in the placebo group ( P < .001). This was supported by the rate of ≥24-week RBC-TI of 28% (95% CI, 20.1 to 37) in the imetelstat group versus 3.3% (95% CI, 0.4 to 11.5) in the placebo group ( P < .001). However, there was no major difference between arms regarding the key secondary end point of erythroid response (HI-E) per International Working Group 2006 criteria or secondary end points reflective of a disease-modifying effect such as complete remission rate and overall survival. The most common adverse reactions were thrombocytopenia, leukopenia, neutropenia, increased liver enzymes, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19, and headache. The rate of grade 3 to 4 neutropenia and thrombocytopenia were 72% and 65%, respectively, in the imetelstat arm compared with 7% and 8% in the placebo arm. Despite the high incidence of neutropenia and thrombocytopenia, the FDA determined that the benefits outweighed the risks in this patient population with high unmet need. Postmarketing requirements were issued to evaluate long-term safety and to conduct a randomized trial comparing at least two dosages of imetelstat to potentially minimize risks of imetelstat treatment and improve tolerability.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Nina Kim
1FDA, Silver Spring, United States
E. Dianne Pulte
2U.S. Food and Drug Administration, Silver Spring, United States
Lori A. Ehrlich
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Alexei C. Ionan
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Spencer Haupert
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Jonathon Vallejo
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Francis Green
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Nan Zheng
Yun Wang
Jiang Liu
Javier G. Blanco
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Sarah E. Dorff
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Brian Booth
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Moran Choe
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Brenda Gehrke
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Vishal Bhatnagar
Marc Theoret
Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD
Richard Pazdur
From the Oncology Center of Excellence (G.U.M., R.P.) and the Office of the Commissioner (N.N.B., R.M.C.), Food and Drug Administration, Silver Spring, MD.
R. Angelo de Claro
Center for Drug Evaluation and Research, Silver Spring, MD
Kelly J. Norsworthy
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD