Elritercept for Transfusion-Dependent Anemia in Lower-Risk MDS: A Trial in Progress

Rami S. Komrokji, MD, Moffitt Cancer Center, Tampa, Florida, presented the design of a phase 3 trial in progress, which is underway to evaluate the efficacy and safety of elritercept, a novel activin receptor type IIA ligand trap, to treat transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS).¹

Myelodysplastic syndromes (MDS) are characterized by defects in hematopoiesis, often leading to anemia and dependence on red blood cell transfusions. Patients with high transfusion burdens face poor prognoses; and existing therapies, including erythropoiesis-stimulating agents and erythroid maturation agents, have limited efficacy in this patient population.

Elritercept is a modified activin receptor type IIA ligand trap designed to inhibit select transforming growth factor-β (TGF-β) superfamily ligands, including activin A, promoting hematopoiesis across multiple progenitor stages. Results from a phase 2 study of patients with MDS indicate that elritercept may restore effective hematopoiesis by enhancing early- and late-stage progenitor cell differentiation.² Preclinical studies suggest additional benefits, including improved iron utilization and reduced inflammation, critical in MDS pathophysiology.³

The global multicenter RENEW trial is a double-blind, placebo-controlled study enrolling adults with very low-, low-, or intermediate-risk MDS per the Revised International Prognostic Scoring System (IPSS-R). A placebo comparator was selected for this first pivotal trial to provide a robust assessment of elritercept and to align with international guidelines for comparator selection, emphasizing the importance of placebo-controlled studies in areas where effective treatments are scarce.

The study plans to enroll 225 patients across 127 sites in 24 countries worldwide. Participants, stratified by ring sideroblast status and baseline transfusion burden, receive elritercept or placebo subcutaneously every 4 weeks. The trial’s primary endpoint is the proportion of participants achieving transfusion independence for eight or more weeks during the first 24 weeks of treatment. Secondary endpoints include transfusion independence for 24 or more weeks and the safety profile of elritercept. Participants will undergo MDS disease assessment every 24 weeks to ensure clinical benefit.

The results of the RENEW trial are expected to support the registration of elritercept for anemia in LR-MDS. By targeting multiple stages of erythropoiesis, elritercept has the potential to provide a novel therapeutic option for patients with limited alternatives.

References

1. Komrokji RS, Diez-Campelo M, Chee LCY, et al. Renew trial in progress: a phase 3, double-blind, placebo-controlled study to evaluate the efficacy and safety of elritercept (KER-050) for the treatment of transfusion-dependent anemia in adult participants with very low-, low-, or intermediate-risk myelodysplastic neoplasms (MDS). Abstract #3228.1. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.
2. Chee L, Ross DM, Cluzeau T, et al. er-050 Treatment reduced iron overload and increased bone specific alkaline phosphatase in participants with lower-risk mds supporting potential to restore balance to the osteohematopoietic niche. Blood. 2023;142(Suppl 1):1089. doi: 1182/blood-2023-186326
3. Moses B, Dills M, Wheeler A, et al. Rker-050, a Modified activin receptor type Iia ligand trap, promoted erythropoiesis in a murine model of myelofibrosis. Blood. 2023;142(Suppl 1):4524. doi: /10.1182/blood-2023-178741