Acceleron Pharma, Inc. announced the initiation of a phase 2 study of its investigational protein therapeutic, ACE-536, to treat anemia in patients with myelodysplastic syndromes (MDS). MDS are a group of hematologic malignancies of the bone marrow that result in low levels of one or more types of blood cells resulting most commonly in severe and chronic anemia (low levels of red blood cells). The company is developing ACE-536 in a global collaboration with Celgene Corporation.

The company earned a $10 million milestone for initiating this phase 2 study and is still eligible to receive development, regulatory and commercial milestones of up to $200 million for the ACE-536 program. The phase 2 clinical trial is designed to evaluate the safety, tolerability and efficacy of ACE-536 in patients with low-risk or intermediate-1 risk MDS. Efficacy measures include increases in hemoglobin levels, reduction of red blood cell transfusion burden, and other hematologic parameters, as well as biomarkers of iron and bone metabolism.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies of the bone marrow commonly leading to severe and chronic anemia due to ineffective erythropoiesis (red blood cell formation). The National Cancer Institute estimates that more than 10,000 people are diagnosed with MDS in the United States each year. Patients with MDS have a hypercellular bone marrow with various dysplastic changes of the cells that are also seen in peripheral blood, resulting in cytopenias (low blood cell counts) and an increased risk of progression to acute myeloid leukemia (AML).

ACE-536 is a modified type II activin receptor fusion protein that acts as a ligand trap for members in the TGF-beta superfamily involved in late stages of erythropoiesis. ACE-536 promotes late-stage erythrocyte precursor cell differentiation, distinct from erythropoietin which acts during early, proliferative stages of erythropoiesis. This mechanism of action to increase red blood cells has the potential to treat patients with anemia in diseases such as myelodysplastic syndromes (MDS) and beta-thalassemia that are inadequately managed with current therapy.

In a phase 1 clinical study of healthy volunteers, ACE-536 produced a dose-dependent increase in red blood cells and hemoglobin levels. Acceleron and Celgene are jointly developing ACE-536 for diseases such as beta-thalassemia and myelodysplastic syndromes (MDS).