Amgen (THOUSAND OAKS, California) announced results from its 24-month, 332-patient phase III pivotal study in women with early and late stage postmenopausal osteoporosis that show twice-yearly subcutaneous injections of denosumab, a fully-human monoclonal antibody that specifically targets RANK Ligand (RANKL, the essential mediator of osteoclasts), increased bone mineral density (BMD) at all sites measured, including in highly cortical areas of the skeleton. RANKL is found in all parts of cortical and trabecular bone. The agent binds RANKL and inhibits osteoclast formation, function, and survival.

Denosumab significantly increased lumbar spine BMD compared with placebo at 24 months (6.5% vs -0.6%, P <.0001) as well as produced significant increases in BMD at the total hip (3.4% vs -1.1%, P <.0001), one-third distal radius (1.4% vs -2.1%, P <.0001), and total body (2.4% vs -1.4%, P <.0001). Time since menopause did not influence BMD response to denosumab.

The overall incidence of adverse events (AEs) was similar between the denosumab and placebo groups. The most common AEs in both treatment groups were arthralgia, nasopharyngitis, and back pain. Serious AEs were reported in 18 subjects (11%) in the denosumab group and in 9 subjects (5.5%) in the placebo group (P = .074). The higher incidence of serious AEs in the denosumab group was primarily due to a greater number of subjects who had infections treated as hospital inpatients (8 denosumab, 1 placebo). However, the overall incidence of infections reported as AEs was balanced between the two groups (60% denosumab, 61% placebo).

Types of infections in the hospitalized subjects included pneumonia, diverticulitis, appendicitis, sepsis, pyelonephritis, urinary tract infection; cellulitis in denosumab subjects and lobar pneumonia in the placebo subject. According to Amgen, none of these infections was considered to be related to denosumab treatment. No opportunistic infections were reported. Amgen expects results in the second half of 2008.

In addition to 4 phase III and 2 phase II trials in postmenopausal osteoporosis, Amgen has evaluated denosumab's effects on bone erosions in rheumatoid arthritis in a phase II study.