Acceleron Pharma, Inc., a biopharmaceutical company, has initiated a phase II study of its investigational protein therapeutic, ACE-536, to treat anaemia in patients with myelodysplastic syndromes (MDS). MDS are a group of haematologic 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 anaemia (low levels of red blood cells).

Acceleron is developing ACE-536 in a global collaboration with Celgene Corporation. Acceleron 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 programme.

“The anaemia experienced by patients with MDS is clinically challenging because it is often unresponsive to administration of erythropoietin and many patients ultimately require red blood cell transfusions,” said Professor Uwe Platzbecker, MD, director outpatient department of Haematology/Oncology at Universitatsklinikum Carl Gustav Carus in Dresden, Germany and coordinating principal investigator of the ACE-536 “PACE-MDS” phase II study. “We are excited to explore ACE-536 as a potential new treatment for MDS patients in this phase II study.”

“ACE-536 has the potential to make a significant impact on the treatment of anemia in MDS,” said Matthew Sherman, MD, chief medical officer of Acceleron. “Unlike erythropoietin, ACE-536 may target the specific defect in the erythropoietic maturation process in MDS patients and we are optimistic that it could become an important new therapeutic option for this underserved patient population.”

The phase II 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 haematologic 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 leukaemia (AML).  Nearly all MDS patients suffer from anaemia. The anaemia in MDS is due to ineffective erythropoiesis, which is characterized by high endogenous levels of erythropoietin driving an abundance of early stage red blood cell precursors and an inability of these precursor cells to properly differentiate into healthy, functional red blood cells. Many patients are therefore unresponsive to the administration of erythropoietin to correct the resulting anaemia and instead require red blood cell transfusions, which can increase the risk of infection and iron-overload related toxicities.

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 I 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).

Acceleron is committed to discover, develop, manufacture and commercialise novel protein therapeutics for orphan diseases and cancer.