Effectiveness
Amgen has reported on two clinical trials that were designed and funded by the company.
In a Phase III clinical trial ('FREEDOM') involving 7,808 women aged 60 to 90, there were significant improvements in the subset of women with more severe disease (two or more prevalent vertebral fractures and/or one or more prevalent vertebral fractures with moderate or severe deformity) at the beginning of the study. Researchers reported a 35% risk reduction with denosumab compared to placebo (17% vs. 49%). Within this subset, only 31% of those taking denosumab developed new vertebral fractures, versus 71% of those receiving placebo.
The second phase III clinical trial involved 1,468 prostate cancer patients receiving hormone-deprivation therapy who were randomized to receive either denosumab or a placebo every 6 months over a 36 month period (all patients also received supplemental calcium and vitamin D). Of those taking the placebo, 3.9% experienced bone fractures during the 36 months, compared with 1.5% of those who received denosumab.
Both studies showed a decrease in fracture rates comparable to those achieved with zoledronic acid and teriparatide, and slightly more than under oral nitrogenous bisphosphonates.
Other studies have been discussed by Baqir and Copeland (Clinical Pharmacist 2010; 2:400), including the DEFEND, DECIDE and STAND trials. one et al. investigated the effects of denosumab on bone mineral density (BMD) in women with BMD T-scores between −1.0 and −2.5 in a randomized trial comparing it with placebo. The primary endpoint was BMD change in the lumbar spine over two years as compared to baseline. The T-score for patients receiving danosumab increased by +6.5%, while the change in patients receiving placebo was −0.6% (ARR =7%; p<0.0001).
Brown et al. compared denosumab with alendronate "head-to-head" using total hip BMD as the primary outcome measure. There were increases in total hip BMD of 3.5% and 2.6% in the denosumab and alendronate groups respectively (ARR =1%; p<0.0001; NNT = 100). Although this study was not adequately powered to compare fracture rates, fractures were reported in 4% of the denosumab group and 3.2% of the alendronate group. Kendler et al. investigated denosumab therapy following on after alendronate. Women on alendronate 70 mg weekly for a "run-in" period of 1 month were then switched to denosumab or maintained on alendroanate (with matching placebo). The primary hypothesis was that denosumab was non-inferior to alendronate, and the primary endpoint was percentage change in total hip BMD at 12 months. BMD increase was +1.9% vs. +1.05% in patients given denosumab vs. those continuing on alendronate (ARR = 0.85%; p<0.0001; NNT = 118). Again, the study was not powered to compare fracture rates, but fractures were reported as adverse events in 8 patients (3.2%) in the denosumab group and 4 patients (1.6%) in the alendronate group.
Read more about this topic: Denosumab