Dr Sekeres on Efforts to Improve Anemia Management Strategies in Lower-Risk MDS

There are 2 studies that have been designed looking at elritercept that essentially have followed the luspatercept playbook.

Mikkael A. Sekeres, MD, MS, a professor of medicine with tenure and chief of the Division of Hematology at Sylvester Comprehensive Cancer Center of the University of Miami Miller School of Medicine, discussed the evolution of anemia management in lower-risk myelodysplastic syndromes (MDS), from erythropoiesis-stimulating agents (ESAs) to luspatercept-aamt (Reblozyl), and the phase 3 development of the investigational activin receptor ligand trap elritercept (KER-050; TAK-226).

Historically, an ESA is often the first agent used for anemia management in patients with lower-risk MDS, Sekeres explained. Serum erythropoietin (EPO) levels tend to be high in these patients because the diseased marrow cannot produce red blood cells (RBCs) to provide negative feedback, he said. Despite this, exogenous EPO works in approximately 40% of patients, particularly those with lower serum EPO levels who are not yet transfusion dependent, he noted.

Luspatercept, which acts on late-stage erythropoiesis through SMAD2/3 signaling, was first approved for use in transfusion-dependent patients with ring sideroblasts or an SF3B1 mutation who had received a prior ESA, according to Sekeres. This agent later gained frontline FDA approval based on data from the phase 3 COMMANDS trial (NCT03682536), which randomly assigned ESA-naive, transfusion-dependent patients to receive luspatercept or epoetin alfa. In the study supporting the frontline approval, luspatercept (n = 86) prevailed against epoetin alfa (n = 48), improving the rate of patients who achieved RBC transfusion independence of at least 12 weeks along with a mean hemoglobin count increase of at least 1.5 g/dL within the first 24 weeks (58.5% vs 31.2%; P < .0001).

Similar to luspatercept, elritercept also targets late-stage erythropoiesis through SMAD2/3 signaling, but as a modified activin receptor ligand trap, it has greater activity against activin A and activin B than luspatercept, Sekeres explained. This investigational agent is currently being evaluated in a pair of phase 3 trials in patients with MDS with anemia, following the same path as the development of luspatercept, he said. The placebo-controlled RENEW trial (NCT06499285) is evaluating elritercept in patients following prior ESA therapy, and the ELRiSE MDS study (NCT07422480) is comparing elritercept directly with epoetin alfa, similar to COMMANDS.