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).
About Amgen
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.
CONTACT: Amgen, Thousand Oaks
Kerry Beth Daly, 516-982-9328 (media)
Arvind Sood, 805-447-1060 (investors)
SOURCE: Amgen