Amgen Inc (THOUSAND OAKS, California) announced findings from its head-to-head, double-blind trial comparing the effects of denosumab in postmenopausal women with low bone mass transitioned from weekly alendronate (Fosamax^®, Merck & Co, Inc) vs continued alendronate therapy on bone mineral density (BMD). The study demonstrated superior results for primary and all secondary endpoints.

The 1-year, nonpivotal, randomized, active controlled, parallel phase III study showed that patients treated with twice-yearly subcutaneous injections of denosumab achieved significantly greater BMD gains at all sites measured including the total hip (primary endpoint), lumbar spine, femoral neck, distal radius, and hip trochanter compared with patients who continued alendronate therapy. The primary endpoint of relative magnitude of BMD improvement at the total hip was ~80% greater in the denosumab versus the alendronate group. The secondary endpoints included evaluation of the effects of transitioning to denosumab compared with continuing alendronate treatment on percent change from baseline in BMD at the lumbar spine, hip trochanter, femoral neck, and distal radius. Eligible patients had T-scores ≤-2 and ≥-4 at the lumbar spine or total hip and had previously been treated with alendronate.

According to Amgen, the incidence and types of adverse events (AEs) observed in the study, including neoplasm and infection, were well balanced between the denosumab and alendronate treatment groups comprising 504 women, with ~250 patients in each arm. The most common AEs across both treatment arms were back pain, arthralgia, and nasal pharyngitis.

Earlier in 2008, the company reported results from its 24-month, phase III, pivotal study in 332 women with early and late-stage postmenopausal osteoporosis showing that twice-yearly subcutaneous injections of denosumab increased BMD at all sites measured, including in highly cortical areas of the skeleton. In the second half of 2008, Amgen expects results of its large, pivotal phase III registrational study that will evaluate denosumab's impact on fracture risk reduction in women with postmenopausal osteoporosis. In addition to four phase III and two phase II trials in postmenopausal osteoporosis, the company has evaluated denosumab's effects on bone erosions in rheumatoid arthritis in a phase II study.

Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand (RANKL), an essential regulator of osteoclasts. RANKL is found in all parts of cortical and trabecular bone. Denosumab binds RANKL and inhibits osteoclast formation, function, and survival. The agent is being studied in a range of bone loss conditions including postmenopausal osteoporosis, rheumatoid arthritis, and cancer treatment-induced bone loss (in breast and prostate cancer patients), as well as for its potential to delay bone metastases and inhibit and treat bone destruction across many stages of cancer.