ACE-661
for Bone Loss Disorders
ACE-661 is an investigational protein therapeutic that increases bone mass and strength by targeting the bone morphogenetic receptor type 1A receptor pathway. Acceleron is developing systemically administered ACE-661 to treat patients with bone loss disorders.
Mechanism of Action
| ACE-661, a novel anabolic bone agent currently in preclinical research, is a protein therapeutic based on the bone morphogenetic protein receptor type 1A (BMPR1A). BMPR1A is a high-affinity receptor for proteins in the TGF-β superfamily that play a role in the development and remodeling of bone. ACE-661 is a soluble fusion protein that binds to these proteins and blocks their signaling through BMPR1A. In normal rodents and in preclinical models of bone loss, systemic administration of a mouse form of ACE-661 resulted in significantly increased bone density, mass and strength. Moreover, ACE-661 exhibited anabolic effects, evidenced by increased osteoblast activity. |
Disease Overview
Bone loss contributes to substantial disability for individuals and economic burdens to society. People who suffer bone loss commonly experience pain and progressive disability that can significantly impair their ability to walk or work, and have both increased risk for, and incidence of fractures. Causes of bone loss include:
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Clinical Need
For patients with osteoporosis, cancer-related bone loss, or treatment-induced bone loss, the mainstay of treatment is with drugs called anti-resorptives, which partially lower the risk of fractures by slowing bone loss. However, patients with prior fractures and extensive damage have a need for anabolic therapies to rebuild and repair bone. Recombinant forms of BMPs are used as alternatives to bone grafts to promote fracture healing and bone growth, but must be applied locally to the injury site and address the needs of only a subset of patients.
The only approved systemically-administered anabolic bone agent is a recombinant form of parathyroid hormone (rPTH), which is effective for men and women with osteoporosis (including induced by chronic use of glucocorticoids) who are at high risk for, or have had a fracture. However, rPTH has several limitations.
rPTH is not recommended for use in patients at increased risk for osteosarcoma, nor for patients with bone metastases or a history of skeletal malignancies. Additionally, the safety and efficacy of rPTH have not been evaluated beyond 2 years of treatment. Consequently, use of the drug for more than 2 years during a patients’ lifetime is not recommended. Finally, rPTH is inconvenient: patients must administer the drug as a daily subcutaneous injection.
There is significant need for broadly applicable, systemic treatments to promote healthy bone growth. ACE-661 represents a novel approach to treating disorders of bone loss.
Clinical Trials
Preclinical and IND-enabling studies of ACE-661 are currently underway.