"These results demonstrate that targeting the RANK ligand pathway with denosumab could represent a promising new approach in two different disease settings characterised by bone loss," says Roland Baron, Professor and Chair of the Department of Oral Medicine, Infection and Immunity at the Harvard School of Dental Medicine.
Denosumab is a fully human monoclonal antibody specific for the RANK ligand. This molecule regulates the formation and activation of osteoclasts, which are responsible for bone resorption-a process that is typically accelerated in osteoporosis. Given as a subcutaneous injection twice a year, denosumab might benefit from greater patient adherence than treatments that need to be administered daily, weekly or monthly.
In the FREEDOM trial, 7868 women received either denosumab or placebo for 3 years.1 Compared with placebo, denosumab cut the risk of vertebral fracture by 68% and the risk of hip fracture by 40%. Bone mineral density increased significantly in women who received the antibody.
The HALT study enrolled 1468 men with non-metastatic prostate cancer who were receiving androgen-deprivation therapy.2 After 2 years, bone mineral density of the lumbar spine in patients who received denosumab was 6.7% higher than that in patients who received placebo. Denosumab was associated with a 62% lower incidence of spine fractures.
Denosumab had a similar adverse effect profile to placebo in both the FREEDOM and HALT studies, although infections were more common in denosumab-treated patients. Investigators observed no cases of osteonecrosis of the jaw in either study.
Another Phase III trial, as yet unpublished, showed that denosumab prevented fractures in patients with bone metastases from breast cancer more effectively than zoledronate, the current standard of care.
Denosumab could be available to prescribe in 2010. Amgen, the antibody's manufacturer, applied in January 2009 for approval to market denosumab in Europe for the three indications studied in the above trials.
Further information: Amgen