Osteoporosis - AMG-162
Bone remodelling is a process that continues throughout a person's life, and if the rate of bone resorption exceeds the rate at which new bone is formed, osteoporosis results, leaving bones increasingly fragile.
Bone remodelling is a process that continues throughout a person's life, and if the rate of bone resorption exceeds the rate at which new bone is formed, osteoporosis results, leaving bones increasingly fragile.
The pro-inflammatory cytokine RANKL - receptor activator of NF-kB ligand - is a tumour necrosis factor which is involved in the bone erosion process, meaning that it is a potentially useful target for novel drugs to treat osteoporosis.
Amgen has developed a fully human monoclonal antibody, AMG-162, which has a high affinity and specificity for RANKL. Its safety and efficacy were investigated in a randomised, double blind placebo-controlled trial in 49 healthy postmenopausal women.1 They were given single subcutaneous doses of 0.01, 0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg of the antibody, or placebo, and followed up for six or nine months.
It was well tolerated, no serious adverse events were observed, and serum concentrations were maintained for up to six months at the highest dose.
A further trial was carried out in a group of 411 postmenopausal women with low bone mineral density.2 In the randomised, double blind placebo-controlled trial, subjects were given 6, 14 or 30 mg of the antibody every three months, or 14, 60, 100 or 210 mg every six months. Some patients were also given oral alendronate once a week. Dose dependent increases in bone mineral density were seen, and after a year all those given the antibody had an increase of 4-7% in lumbar spine bone mineral density. It was well tolerated, and a Phase III study is being carried out. It is also in Phase II trials for rheumatoid arthritis and metastatic bone disease.