Amgen Inc (THOUSAND OAKS, California) announced findings from a head-to-head, double-blind study comparing the effects of twice-yearly subcutaneous injections of denosumab (a fully human monoclonal antibody that specifically targets RANKL) versus weekly oral doses of alendronate (Fosamax®, Merck & Co, Inc) in postmenopausal women with low bone mineral density (BMD). The study met primary and all secondary endpoints.

In the 1-year, nonpivotal study, 1189 women with postmenopausal osteoporosis were randomized 1:1 to receive denosumab or alendronate and followed for 1 year to assess changes in BMD. The primary endpoint was to evaluate denosumab compared with alendronate on percentage change from baseline in BMD at the total hip. Secondary endpoints were to compare the two drugs' effect on percentage change from baseline in BMD at the lumbar spine, hip trochanter, femoral neck, and distal radius.

Denosumab treatment achieved significantly greater BMD gains at the total hip, hip trochanter, and distal radius compared with alendronate. For the primary endpoint, the relative magnitude of BMD improvement at the total hip was ~40% greater in the denosumab versus the alendronate group. The changes in BMD in the alendronate group were consistent with previously reported studies. The complete analysis of data from this trial will be presented in a peer-reviewed forum later in 2008.

The incidence and types of adverse events observed in this study were similar between the two treatment groups, with the most common adverse events being arthralgia, back pain, constipation, and dyspepsia.

RANKL is an essential mediator of osteoclasts, and denosumab inhibits all stages of osteoclast activity. The agent is being studied in a range of bone loss conditions including postmenopausal osteoporosis, rheumatoid arthritis, cancer treatment-induced bone loss, as well as for its potential to delay bone metastases and inhibit and treat bone destruction across many stages of cancer. A large, pivotal phase III study evaluating the ability of denosumab to reduce fracture risk in women with postmenopausal osteoporosis is ongoing.