The FINANCIAL — Amgen and UCB on October 12 presented additional findings from an exploratory sub-study of the previously reported romosozumab Phase 2 trial. The findings were presented on October 12 in an oral plenary session at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting in Seattle.
The small exploratory sub-study data showed that, at month 12, the investigational bone-forming agent romosozumab increased estimated bone strength (percent change from baseline) at the spine and hip more than open-label teriparatide in postmenopausal women with low bone mass. These results were measured by a validated method called finite element analysis (FEA), which utilized quantitative computed tomography (QCT) scans to simulate compression overload to estimate vertebral strength, and a sideways fall to estimate femoral strength, according to Amgen.
“Engineers and physicists have long used finite element analysis to better understand the structural integrity and failure of physical objects when subjected to load,” said lead investigator Tony M. Keaveny, Ph.D., professor of Mechanical Engineering and Bioengineering at the University of California, Berkeley. “By applying this analysis to bone scans of postmenopausal women with low bone mass, we were able to integrate the information we had on bone mineral density and structure to estimate bone strength in those treated with romosozumab.”
The FEA showed that, at the spine, women in the romosozumab group (210 mg once monthly, n=24) increased estimated strength compared to baseline by 27.3 percent at month 12, which was greater than placebo (–3.9 percent, n=27) and teriparatide (18.5 percent, n=28).2 At the hip, the estimated strength increased from baseline by 3.6 percent with romosozumab (n=9), compared with placebo (-0.1 percent, n=18) or teriparatide (-0.7 percent, n=19).
These data are from a small exploratory sub-study (n=79) of a Phase 2 trial (NCT00896532) that included a total of 419 patients. A subset of these women underwent spine and hip QCT imaging to measure bone mineral density (BMD) gains.3 To investigate the effects of romosozumab on bone strength an FEA was performed on these QCT scans.
“The strength improvements observed with romosozumab in this trial – and documented using a validated method for assessing fracture risk and monitoring treatment – further support its potential as a treatment option for patients at high risk for fracture,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “These important new data support our extensive global Phase 3 program of romosozumab, and we look forward to advancing this research to help provide a potential new treatment option for appropriate patients.”
Adverse events in the original Phase 2 study were similar across groups, except for mild, generally non-recurring injection site reactions observed more frequently with romosozumab compared to placebo, but with no observed dose-related relationship. The most common adverse events included mild upper respiratory tract infection, pain in the back and joints, and headache. These reactions did not lead to study drug discontinuation or study withdrawal; the safety of romosozumab will be further addressed in subsequent larger studies.
“These data illustrate the potential impact of building bone through both increasing bone formation and decreasing bone resorption as romosozumab has demonstrated in skeletal regions of interest. These sub-study results reinforce our confidence in the ability of romosozumab to build bone strength as well as density and we look forward to reporting the outcomes of the first fracture study in 2016,” said Professor Dr. Iris Loew-Friedrich, chief medical officer and executive vice president at UCB.