Biopharmaceutical company, Acceleron Pharma, Inc. has presented data on Haemoglobinopathies and rare anaemias in Limassol, Cyprus, demonstrating positive effects of ACE-536 to treat both the severe anaemia and serious organ damage due to iron overload in a preclinical model of beta-thalassemia. Acceleron is developing ACE-536 in collaboration with Celgene. The data was presented at the 3rd Pan-European Conference.

Beta-thalassemias are a group of hereditary blood disorders characterized by anemia that results from defective haemoglobin beta chain synthesis and ineffective red blood cell (RBC) production. Haemoglobin is the iron-containing molecule in red blood cells that carries oxygen to cells throughout the body. Depending on disease severity and treatment, beta-thalassemic individuals often experience pale skin, weakness, fatigue as well as additional serious health effects, including splenomegaly (enlargement of the spleen), reduced growth, skeletal changes that result from expansion of the bone marrow and organ damage due to iron overload.

In a preclinical mouse model of beta-thalassemia intermedia, ACE-536 significantly increased levels of RBCs and haemoglobin by promoting the differentiation of late stage RBC precursors. Consistent with its ability to correct ineffective RBC production and anaemia, ACE-536 reduced levels of erythropoietin (EPO) in the blood. ACE-536 also substantially reduced the size of the enlarged spleens of the beta thalassemic mice. Additionally, ACE-536 restored iron metabolism as evidenced by reduced serum ferritin and increased hepcidin levels, leading to reduced iron deposition in the spleen, liver and kidney.

“These beta-thalassemic mice are an excellent preclinical model of beta-thalassemia, reproducing the numerous, life-threatening clinical complications experienced by patients who suffer from this disease,” said Ravi Kumar, chief scientific officer of Acceleron. “We are excited by these data which show the potential of ACE-536 to substantially alleviate the anaemia and iron overload characteristic of the disease and look forward to initiating a phase II trial of ACE-536 in patients with beta-thalassemia in the next few months.”

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

Acceleron is a privately-held biopharmaceutical company committed to discover, develop, manufacture and commercialize novel protein therapeutics for orphan diseases and cancer.