for Rare Anemia Indications

ACE-536 is an investigational protein therapeutic that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily.  Acceleron and Celgene are developing ACE-536 to treat anemia in patients with rare blood disorders, including β-Thalassemia and myelodysplastic syndromes .

  • 25 Trillion

    Average number of RBCs in normal adult circulation at any given time, accounting for roughly 25% of total body cell number.

Mechanism of Action

ACE-536 is a ligand trap that inhibits members of the TGF-β superfamily involved in late stages of erythropoiesis.  Sotatercept and ACE-536 are biochemically distinct molecules and may have unique pharmacological attributes that enable their preferential use in particular anemia indications.  Notably, unlike sotatercept, ACE-536 does not bind with high affinity to activin A.  In preclinical studies, ACE-536 promoted RBC formation in the absence of erythropoietin (EPO) signaling, had distinct effects from EPO on RBC differentiation, and acted on a different population of progenitor blood cells than EPO during RBC development.  In these studies, ACE-536 did not promote significant increases in bone mass.

Disease Overview

Anemia, a deficiency of RBCs, is a debilitating condition that impairs function and quality of life for people affected by a number of rare blood disorders.

For people with many of these rare blood disorders, chronic blood transfusions are the standard of care.  Recombinant growth factors called erythropoietin stimulating agents (ESAs), which are widely used to treat more common forms of anemia (e.g., due to chronic kidney disease), are inappropriate or ineffective for many rare blood disorders and thus there is significant need for novel therapies for these patients.

Clinical Need

ACE-536 increases RBC levels in a way that is fundamentally distinct from ESAs. By affecting production of red blood cells by a mechanism distinct from ESAs, ACE-536 has the potential to treat anemia in patients for whom ESAs are ineffective or inappropriate.

Clinical Trials

In a phase 1 study in healthy volunteers, ACE-536 produced a dose-dependent increase in RBC and hemoglobin levels. These clinical results and the observed increases in RBC parameters from several preclinical animal models suggest that ACE-536 could be a meaningful novel therapy to treat anemia.  Acceleron and Celgene are developing ACE-536 in two phase 2 clinical trials to treat anemia in diseases in which erythropoiesis-stimulating agents are either not approved or are not well-suited to treat the underlying anemia.

• Phase 2 Study of ACE-536 to Treat Patients with Beta-Thalassemia Intermedia.   For information on this trial, please click here

• Phase 2 Study of ACE-536 for the Treatment of Anemia in Patients with Myelodysplastic Syndrome.   For information on this trial, please click here