Acceleron Developing Thalassemia Treatments
January 28, 2013 – Acceleron, a biopharmaceutical company based in Cambridge, Massahusetts, in collaboration with Summit, New Jersey-based pharmaceutical partner Celgene Corporation, is developing two programs, sotatercept (formerly called ACE-011) and ACE-536, for the treatment of beta-thalassemia.
Sotatercept and ACE-536 are biologic drugs that increase hemoglobin and red blood cells levels by promoting the maturation of late-stage red blood cell precursors into functional red blood cells. Both sotatercept and ACE-536 target molecules involved in the later-stages of erythropoiesis (red blood cell formation) and work via a mechanism that is distinct from erythropoietin (EPO), which acts during early, proliferative stages of erythropoiesis. Sotatercept and ACE-536 utilize a novel approach to treat anemia caused by ineffective erythropoiesis.
In preclinical animal studies, sotatercept and ACE-536 increased RBC levels in normal mice and monkeys. In a preclinical mouse model of beta-thalassemia intermedia, ACE-536 significantly increased levels of RBCs and hemoglobin by promoting the differentiation of late stage RBC precursors. Consistent with its ability to correct ineffective RBC production and anemia, 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 improved iron metabolism as evidenced by reduced serum ferritin and increased hepcidin levels, leading to reduced iron deposition in the spleen, liver and kidney (data presented at the 3rd Pan-European Conference on Hemoglobinopathies and Rare Anemias in Limassol, Cyprus).
Both sotatercept and ACE-536 have been studied in human clinical trials and were generally well tolerated and induced robust increases in hemoglobin and hematocrit levels. Both drugs are now being studied in phase 2 clinical trials to treat patients with beta-thalassemia.
Alexis Thompson, MD, MPH, a member of the CAF Medical Advisoy Board, states that “these could potentially be very useful agents for patients with non-transfusion-dependent thalassemia. The pre-clinical laboratory and animal data thus far suggest that these drugs work on improving red cell production by promoting maturation of red blood cells and possibly reducing the globin chain imbalance, addressing some of the fundamental problems that contribute to anemia and impaired red cell survival in thalassemia. Early clinical trials in Europe are promising. If successful, this could be an exciting development for some patients with thalassemia intermedia.”
The titles of the trials for these two drugs are:
- A Phase 2a, Open-Label, Dose Finding Study to Determine the Safety and Tolerability of Sotatercept in Adults With Beta-Thalassemia (www.clinicaltrials.gov identifier NCT01571635)
- A Phase 2a, Open-Label, Ascending Dose Study to Evaluate the Effects of ACE-536 in Patients with Beta-Thalassemia Intermedia (www.clinicaltrials.gov identifier NCT01749540)
More information on these programs and Acceleron Pharma can be found at www.acceleronpharma.com.