AMG-162 Treatment of Osteoporosis Bone Cancer Therapy Treatment of Rheumatoid Arthritis Human Anti-RANKL Monoclonal Antibody

摘要

Receptor activator of NF-KB ligand (RANKL) is a critical factor in the differentiation and activation of osteoclasts. As a fully human monoclonal antibody to RANKL, AMG-162 binds to RANKL with high affinity and has potential application as a bone antiresorptive agent for the treatment of bone disorders, including osteoporosis and bone metastasis. In cynomolgus monkeys, subcutaneous administration of AMG-162 resulted in highly significant and dose-dependent reductions in serum and urine markers of bone resorp-tion and formation compared with control groups. A significant and dose-dependent increase in bone mineral density was also observed. In postmenopausal women, rapid, dose-dependent and sustained decreases in urinary and serum markers of bone resorption were observed, and in women with low bone mineral density, increases of 4-7% were evident 12 months after initiation of treatment. AMG-162 is in phase III development for the treatment of osteoporosis in postmenopausal women, as well as phase II testing for its potential in metastatic bone disease and rheumatoid arthritis.