Amgen Inc (THOUSAND OAKS, California) announced positive top-line findings from a pivotal phase III placebo-controlled trial evaluating denosumab, the first fully human monoclonal antibody in late-stage clinical development that specifically targets RANK Ligand (the essential regulator of osteoclasts), in the treatment of bone loss in men undergoing androgen deprivation therapy (ADT) for nonmetastatic prostate cancer. The study involved >1400 men, in whom denosumab treatment produced statistically significantly greater increases in bone mineral density (BMD) at the lumbar spine (primary endpoint) and nonvertebral sites compared with placebo at multiple time points. The improvements in BMD were consistent with those seen in other denosumab studies evaluating BMD in women with breast cancer receiving aromatase inhibitor therapy and in postmenopausal women with low bone mass.

During the 36-month evaluation period, men receiving the drug experienced less than half the incidence of new vertebral fractures (a secondary endpoint) compared with those receiving placebo, a statistically significant finding. Furthermore, in the denosumab arm there were fewer nonvertebral fractures over the 36-month period. The incidence and types of adverse events observed in the study were generally similar between both treatment groups. Serious adverse infectious events occurred in ~5% of men receiving placebo treatment as compared with ~6% of those receiving denosumab.

The study demonstrated the potential benefit the drug may represent to prostate cancer patients undergoing ADT for whom bone loss and fractures are serious and underrecognized complications of cancer treatment.

With >19,000 patients participating in trials across indications worldwide, the denosumab development program is the largest ever initiated by Amgen. The company is studying the drug in numerous tumor types across the spectrum of cancer-induced bone disease. There are >11,000 patients currently enrolled in denosumab oncology clinical trials testing the drug for cancer treatment-induced bone loss in breast and prostate cancers, for the prevention of skeletal related events due to the spread of cancer to the bone in multiple myeloma and multiple solid tumors, and for its potential to delay bone metastases in prostate cancer.