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Dalantercept

for Advanced / Metastatic Cancer

Dalantercept (ACE-041) is an investigational protein therapeutic that inhibits angiogenesis by preventing BMP9 and BMP10, proteins in the TGF-β superfamily, from interacting with activin receptor-like kinase 1 (ALK1), a cell-surface receptor found on proliferating endothelial cells.   Dalantercept inhibits ALK1 signaling, which is required for the development of mature, functional vasculature.  Acceleron is developing dalantercept for the treatment of patients with advanced cancer who have failed prior therapy.

  • $10.2 B

    2013 WW sales of angiogenesis inhibitors approved for cancer indications (EvaluatePharma)

Mechanism of Action

Many types of tumors depend on the growth of new blood vessels, a process called angiogenesis, to supply nutrients and oxygen that allows cancer cells to grow, invade nearby tissue, and spread to other parts of the body. Angiogenesis inhibition is a widely-used approach to cancer treatment. Several angiogenesis inhibitors that work by blocking the vascular endothelial growth factor (VEGF) pathway are approved or are in development. Dalantercept is a first-in-class angiogenesis inhibitor with a mechanism distinct from VEGF inhibition. Dalantercept is a soluble form of the activin receptor-like kinase 1 (ALK1) that binds to the TGF-β superfamily members BMP9 and BMP10 and prevents these proteins from signaling through ALK1. ALK1 is expressed on activated blood vessel cells and plays critical roles in the formation and maturation of blood vessels. Acceleron and independent academic collaborators have conducted studies with dalantercept in animal models, demonstrating robust anti-angiogenic and anti-tumor properties in a range of tumor types, including those resistant to VEGF inhibitors.

Disease Overview

Cancer is a leading cause of death and is characterized by the uncontrolled growth and spread of abnormal cells. Many types of tumors depend on the growth of new blood vessels (angiogenesis) to supply adequate nutrients and oxygen, allowing cancer cells to grow, invade nearby tissue, and spread to other parts of the body. Several angiogenesis inhibitors that work by inhibiting the vascular endothelial growth factor (VEGF) pathway are approved or are in development. These therapies, given alone or in combination with chemotherapy and/or radiation, can significantly improve survival. Accordingly, they play an important role in the treatment of advanced solid tumors, including those occurring in the lung, colon/rectum, liver and kidney.  Dalantercept inhibits angiogenesis through a mechanism distinct from VEGF inhibition and may be effective either alone or in combination with existing therapies to treat advanced solid tumors.

Clinical Need

Despite their clinical utility, there are several limitations to approved angiogenesis inhibitors that target VEGF. Most patients with advanced cancers who are treated with VEGF-targeting therapies eventually develop resistance and experience tumor progression, often within several months of initiating therapy. Moreover, some patients are poor candidates for these therapies or must discontinue treatment because of side effects. There is a need for novel therapies that utilize alternative strategies to target the tumor blood supply. Dalantercept represents a new approach to angiogenesis inhibition.

Clinical Trials

Indications of anti-tumor and anti-angiogenic activity observed in the Phase 1 study combined with results from preclinical pharmacology studies suggest that dalantercept has significant potential as an anti-cancer therapy. Several Phase 2 clinical studies of dalantercept in patients with advanced cancers are ongoing in the United States. For more information about these studies, please click on the links below.

• Phase 2 Study of dalantercept (ACE-041) in Patients with Squamous Cell Carcinoma of the Head and Neck.  For more information on this trial, please click here

• Phase 2 study of dalantercept in combination with axitinib in Patients with Renal Cell Carcinoma. For more information on this trial, please click here

• Phase 2 Study of dalantercept in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.  For more information on this trial, please click here