ACE-011 (Treatment of Anemia)

ACE-011 is a novel, first-in-class therapy being developed for the treatment of chemotherapy-induced anemia. ACE-011 works by targeting members of the TGF-β superfamily that signal through the activin receptor type IIA (ActRIIA), and has demonstrated robust increases in hemoglobin and red blood cell (RBC) levels in Phase I studies. In these studies, ACE-011 also promoted new bone formation and increased bone mineral density (BMD). In nonclinical studies of cancer, ACE-011 inhibited tumor growth and metastases.

ACE-011: An Inhibitor of ActRIIA Signaling

ACE-011 is a fully human, soluble fusion protein derived from the extracellular domain of Activin Receptor Type IIA (ActRIIA). Acceleron scientists have engineered the product to combine the portion of ActRIIA that binds tightly to activin along with a component of an antibody molecule. This allows ACE-011 to circulate freely throughout the body (see figure)

ACE-011 is a Novel, First-in-Class Anemia Therapy

ACE-011 binds to and prevents members of the TGF-β superfamily from signaling through activin receptor type IIA (ActRIIA). ACE-011 is the first agent to demonstrate increases of hemoglobin levels and RBCs in humans by targeting signaling by the TGF-β superfamily. ACE-011 is not an erythropoietin (EPO)-based product or EPO-mimetic, does not bind the EPO receptor, but rather targets a pathway that is fundamentally distinct from EPO.

ACE-011 Also Promotes New Bone Formation

Increased ActRIIA signaling suppresses activity of cells responsible for building bone (osteoblasts) and stimulates cells responsible for breaking down bone (osteoclasts). Blocking ActRIIA signaling reverses this effect, thereby enabling the formation of new bone, and increasing bone mass, quality, and mechanical strength:

In Phase 1 clinical studies in healthy post-menopausal women, ACE-011 showed an encouraging safety profile, increased bone formation biomarkers, and significantly increased total hip bone mineral density (BMD).

Clinical Importance of ACE-011

Anemia is one of the most common and debilitating complications associated with cancer chemotherapy, which depletes and prevents formation of red blood cells, and leads to incapacitating fatigue and weakness. The vast majority of therapies approved and in development for anemia target the erythropoietin pathway. However, recent studies have suggested an increased risk of mortality associated with this class of therapy, arising from exposure to high levels of recombinant erythropoietin and its derivatives, which may stimulate tumor progression and increase the occurrence of thromboembolic events.

Many of these patients also suffer from skeletal complications when tumors metastasize to the bone. Although anti-resorptive agents can slow the further deterioration of bone, there are currently no therapies that promote formation of new bone and the repair of pre-existing damage.

The unique pharmacology of ACE-011 will enable it to treat multiple facets of cancer: anemia caused by chemotherapy, malignant bone disease, and the underlying tumor itself. ACE-011 is currently being studied in two Phase 2 clinical trials in cancer patients and is being jointly developed by Acceleron and Celgene Corporation. For information on participating in this study, please click here.

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