Denosumab Osteoporosis Study Meets Primary and All Secondary Bone Mineral Density Endpoints in Alendronate (FOSAMAX(R)) Transition Study
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 percent 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.
Osteoporosis: Impact and Prevalence
Often referred to as the "silent epidemic," osteoporosis is a global problem that is increasing in significance as the population of the world both increases and ages. The World Health Organization (WHO) has recently identified osteoporosis as a priority health issue along with other major non-communicable diseases.
Although fractures to the vertebrae and hip are the most commonly discussed osteoporotic fractures, they do not account for the majority of fractures. In fact, fractures at skeletal sites such as the wrist, pelvis, humerus, clavicle, femur, and lower leg (tibia/fibula) make up an estimated 59 percent of all osteoporotic fractures in the United States (U.S.)(i).
The economic burden of osteoporosis is comparable to that of other major chronic diseases; for example, in the U.S. the costs associated with osteoporosis-related fractures are equivalent to those of cardiovascular disease and asthma(ii)(iii)(iv). It has been reported that osteoporosis results in more hospital bed-days than stroke, myocardial infarction or breast cancer(v).
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FOSAMAX is a registered trademark of Merck & Co., Inc.
(i) Johnell O, Kanis JA. Osteoporosis Int. 2006; 17:1726-1733.
(ii) Burge R, et al. J Bone Miner Res. 2007; 22:465-475
(iii) "Osteoporosis Fast Facts." Washington (DC): National Osteoporosis Foundation. Accessed at http://www.nof.org/osteoporosis/stats.html.
(iv) "Economic Cost of Cardiovascular Diseases." Dallas (TX): American Heart Association. Accessed at http://www.americanheart.org/statistics/10econom.html.
(v) Lippuner K, et al. "Incidence and direct medical costs of hospitalisations due to osteoporotic fractures in switzerland." Osteoporosis International. 1997; 7:414-25.
Amgen, Thousand Oaks
Kerry Beth Daly, 516-982-9328 (media)
Arvind Sood, 805-447-1060 (investors)
Posted: May 2008