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LUSPATERCEPT

for Rare Anemia Indications

Luspatercept (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 luspatercept 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

Luspatercept (ACE-536) is a ligand trap that inhibits members of the TGF-β superfamily involved in late stages of erythropoiesis.  Sotatercept and luspatercept are biochemically distinct molecules and may have unique pharmacological attributes that enable their preferential use in particular anemia indications.  Notably, unlike sotatercept, luspatercept does not bind with high affinity to activin A.  In preclinical studies, luspatercept promoted red blood cell (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, luspatercept did not promote significant increases in bone mass.

Disease Overview

Anemia, a deficiency of red blood cells, 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

Luspatercept increases red blood cell levels in a way that is fundamentally distinct from erythropoiesis stimulating agents (ESAs). By affecting production of red blood cells by a mechanism distinct from ESAs, luspatercept 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, luspatercept 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 luspatercept could be a meaningful novel therapy to treat anemia.  Acceleron and Celgene are developing luspatercept 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 luspatercept (ACE-536) to Treat Patients with Beta-Thalassemia Intermedia.   For information on this trial, please click here

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