Amgen announced findings from a head-to-head, double-blind trial comparing the effects of denosumab in post-menopausal women with low bone mass transitioned from weekly alendronate (Fosamax) versus continued alendronate therapy on bone mineral density (BMD). The study demonstrated superior results for the primary and all secondary endpoints.
In this one-year, non-pivotal phase 3 study, the group 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 the group that continued on alendronate. For the primary endpoint, the relative magnitude of BMD improvement at the total hip was approximately 80 per cent greater in the denosumab versus the alendronate group.
The incidence and types of adverse events observed in this study, including neoplasm and infection, were well-balanced between the denosumab and alendronate treatment groups. The most common adverse events across both treatment arms were back pain, arthralgia, and nasal pharyngitis.
"This is the second phase 3 head-to-head study demonstrating that administration of denosumab resulted in superior BMD gains versus those achieved with alendronate," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "Particularly important was the finding that in this population that had previously been treated with alendronate, patients transitioned to denosumab achieved greater BMD gains than those continuing on alendronate therapy."
This was a randomized, double-blind, active controlled, parallel group study. Eligible patients had T-scores of less than or equal to -2.0 and greater than or equal to -4.0 at the lumbar spine or total hip and had previously been treated with alendronate. A total of 504 women with low BMD participated in the study, with approximately 250 patients in each arm.
The study's primary endpoint was to evaluate the effect of denosumab treatment (twice yearly 60 mg) on total hip BMD in women with low bone mass compared to that in patients continuing alendronate therapy (weekly 70 mg) at 12 months. The secondary endpoints included evaluation of the effects of transitioning to denosumab compared to continuing treatment with alendronate on percent change from baseline in BMD at the lumbar spine, hip trochanter, femoral neck, and distal radius.
Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone). Denosumab is being investigated for its potential to inhibit all stages of osteoclast activity through a targeted mechanism. Denosumab is being studied in a range of bone loss conditions including post-menopausal osteoporosis, rheumatoid arthritis, and cancer treatment-induced bone loss (in breast cancer 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.
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient.