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Pivotal Phase 3 Data Show Denosumab Increased Bone Density at Multiple Skeletal Sites in Early and Later Stage Postmenopausal Women
Overall Incidence of Adverse Events Similar Between Denosumab and Placebo Groups
THOUSAND OAKS, Calif.--(BUSINESS WIRE)--April 2, 2008--Amgen (NASDAQ: AMGN) today announced the publication of results from its 24-month, 332-patient Phase 3 pivotal study in women with early and late stage postmenopausal osteoporosis in the Journal of Clinical Endocrinology and Metabolism.
In this Phase 3 study, twice-yearly subcutaneous injections of denosumab increased bone mineral density (BMD) at all sites measured, including in highly cortical areas of the skeleton. Cortical bone comprises 75 percent of skeletal mass and is a primary determinant of overall strength in vertebral and non-vertebral sites throughout the skeleton.
Denosumab treatment significantly increased lumbar spine BMD compared with placebo at 24 months (6.5 percent vs. -0.6 percent; P less than 0.0001). Denosumab also produced significant increases in BMD at the total hip (3.4 percent vs. -1.1 percent; P less than 0.0001), 1/3 distal radius (wrist) (1.4 percent vs. -2.1 percent; P less than 0.0001), and total body (2.4 percent vs. -1.4 percent; P less than 0.0001). Time since menopause did not influence the BMD response to denosumab.
Denosumab is an investigational fully-human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, the essential mediator of osteoclasts (the cells that break down bone). RANK Ligand is found in all parts of cortical and trabecular bone.
"The effect of denosumab on wrist BMD - reinforced by the BMD increases at the total body and hip regions - suggests denosumab has a positive effect on highly cortical sites," said Javier San Martin, Global Development Lead for the denosumab osteoporosis program. "It appears that RANK Ligand inhibition results in a pattern of effects on cortical bone that may be beneficial."
The overall incidence of adverse events was similar between the denosumab and placebo groups. The most common adverse events in both treatment groups were arthralgia, nasopharyngitis, and back pain.
Serious adverse events were reported for 18 subjects (11 percent) in the denosumab group and 9 subjects (5.5 percent) in the placebo group (P = 0.074). The higher incidence of serious adverse events in the denosumab group was primarily due to a greater number of subjects who had infections treated as hospital inpatients (8 denosumab, 1 placebo). However, the overall incidence of infections reported as adverse events was balanced between the two groups (60 percent denosumab, 61 percent placebo).
Types of infections in the hospitalized subjects included pneumonia, diverticulitis, appendicitis, sepsis, pyelonephritis, urinary tract infection, and cellulitis in denosumab subjects, and lobar pneumonia in the placebo subject. No opportunistic infections were reported. None of these infections were considered by the site investigators to be related to denosumab treatment. The infections were common for this subject population and responded to standard antibiotic therapy.
Amgen expects the results of its large, pivotal Phase 3 registrational study, which will evaluate denosumab's impact on fracture risk reduction, in women with postmenopausal osteoporosis, in the second half of this year.
Denosumab: Clinical Studies in Bone Loss
Underscoring Amgen's commitment to science, its researchers have created a robust clinical program for denosumab as they explore the bone biology of various diseases associated with the RANK Ligand pathway. In addition to four Phase 3 and two Phase 2 trials in postmenopausal osteoporosis, Amgen has evaluated denosumab's effects on bone erosions in rheumatoid arthritis in a Phase 2 study. In the oncology setting, researchers are evaluating denosumab in four Phase 3 and two Phase 2 studies in advanced cancer patients with, or at risk for, bone metastases. In a Phase 2 study, they evaluated denosumab as a possible treatment for patients with multiple myeloma.
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).
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. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
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(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.
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