Amgen Presents Denosumab and Sclerostin Antibody Data at American Society for Bone and Mineral Research Annual Meeting; Data Suggest the Potential for Targeting the Key Proteins, RANK Ligand and Sclerostin, for Bone Loss Conditions
PHILADELPHIA--(BUSINESS WIRE)--Sept. 19, 2006--Amgen
(NASDAQ:AMGN), the world's largest biotechnology company, announced
today the presentation of data at the American Society for Bone and
Mineral Research (ASBMR) Annual Meeting highlighting its expertise in
bone biology research and commitment to developing therapies that
address the burden of bone disease. The studies evaluated denosumab
and a sclerostin antibody, two of the company's investigational
therapies. These antibodies target key proteins responsible for the
regulation of bone destruction and formation.
"Amgen scientists are committed to fulfilling the promise of
biotechnology by developing novel therapeutics aimed at improving bone
health," said Willard Dere, M.D., senior vice president of Global
Development and chief medical officer, Amgen. "Our research has the
potential to transform the scientific understanding of bone biology
and the treatment of conditions associated with bone loss."
Denosumab is an investigational fully human monoclonal antibody
that targets RANK Ligand, a primary mediator of the formation,
function and survival of osteoclasts (cells which resorb or break down
bone). Denosumab is the first therapy in late stage development that
targets RANK Ligand.
Results from a post-hoc exploratory analysis of an ongoing,
multicenter, Phase 2 study, showed that subjects treated with
denosumab subcutaneously, 60 mg twice yearly for up to 24 months,
experience an improvement not only in bone mineral density (BMD) but
also in parameters of hip structural analysis (HSA), a technique that
estimates geometric properties of bone strength.
In the study, patients were evaluated with dual energy X-ray
absorptiometry (DXA), the recognized measure for BMD. The DXA scans
were then analyzed with HSA software, providing an estimated
measurement of bone geometry. Specifically, denosumab therapy resulted
in a 6.69 percent increase in the measure of cortical thickness at the
femoral shaft; there was a 0.31 percent decrease, from baseline, in
the placebo group (p less than 0.001). In the open label alendronate
cohort, there was a 1.82 percent increase in cortical thickness at the
femoral shaft (p less than 0.041). These results are consistent with
previous reports highlighting the effects of denosumab at highly
cortical sites; cortical bone, the dense outer shell of the skeleton,
comprises approximately three-quarters of the total skeletal mass. The
full data from this study will be presented at the ASBMR meeting on
"Increasing thickness at highly cortical sites is an effective way
to improve bone strength and mechanical integrity of the skeleton,"
said Thomas Beck, ScD, associate professor, The Johns Hopkins
University. "These observations support the potential of targeting
RANK Ligand to improve bone structural strength."
This analysis extended the previously-reported two-year results
that demonstrated twice-yearly subcutaneous injections of denosumab
(60 mg) increased BMD at the lumbar spine (7.4 percent), total hip
(5.1 percent), femoral neck (4.6 percent), distal 1/3 radius (1.8
percent) and total body (2.6 percent) compared to placebo at 24
months. Per protocol, the study concluded at 12 months; the post-12
month analyses are exploratory.
Amgen is also reporting on preclinical data for denosumab at the
meeting. In this study, designed to evaluate the effects of denosumab
administration in aged primates after estrogen depletion (OVX),
researchers found that long-term denosumab administration (16 months)
is associated with increases in the mass and density of cancellous and
Sixteen monthly injections of denosumab at 50 mg/kg resulted in
significant increases from baseline in lumbar BMD (+12 percent); the
OVX arm resulted in a -4.9 percent change and sham resulted in a +0.8
percent change in lumbar BMD (p less than 0.001 for both groups).
Total hip BMD was also increased with denosumab treatment (+7.4
percent); the OVX arm experienced a -7.4 percent change and the sham
group experienced a -0.6 percent change in total hip BMD (p less than
0.01 for both groups). Cortical bone mass (volumetric bone mineral
content (BMC) measured by pQCT/ peripheral quantitative computed
tomography) increased at the radial diaphysis with denosumab treatment
(+1.3 percent); the OVX arm had a -5.6 percent change (p less than
0.001) and sham a -2.3 percent change (p less than 0.05).
In the osteoporosis setting, denosumab is being investigated as a
twice-yearly subcutaneous injection and appears well-tolerated in
clinical trials to date. Occurrence of adverse events in a
multicenter, Phase 2 dose-ranging trial was similar among the
denosumab-, placebo-, and alendronate-treated groups with the
exception of dyspepsia, which was more common among those receiving
alendronate. The most common adverse events among all groups were
upper respiratory infection, joint pain, sore throat, back pain, and
headache. To date, no neutralizing antibodies have been observed and
there have been no gastrointestinal or renal effects.
Data for an Investigational Antibody Targeting Sclerostin
A sclerostin-neutralizing monoclonal antibody is being developed
by Amgen and UCB, a Belgian-based biopharmaceutical company.
Sclerostin, a naturally occurring protein in the body, plays a
critical role in controlling bone mass by inhibiting the activity of
bone-forming cells called osteoblasts. The investigational sclerostin
antibody targets this key inhibitor of bone-forming cells.
In data featured at the annual ASBMR meeting, scientists presented
preclinical results from a small study in which three
sclerostin-neutralizing monoclonal antibodies were tested in primates.
The goal of the study was to evaluate the effects of sclerostin
inhibition on bone and bone biology in young female cynomolgus
monkeys. Sclerostin-neutralizing antibodies were administered at 3, 10
and 30 mg/kg once-monthly over a two-month period. Specific results in
this particular study for the sclerostin antibody under development
included increased total BMC at the distal radius (20 percent increase
in BMC for the sclerostin antibody-treated, 10 mg/kg dose group at the
two-month time point versus a one percent increase in BMC for the
vehicle control group). In relation to the vehicle control group,
there was a 5.5-fold increase in the rate of bone formation in lumbar
vertebrae for the sclerostin antibody-treated 30 mg/kg dose group in
the first month. By the end of the two-month study, the strength of
lumbar vertebrae increased for the sclerostin antibody-treated, 30
mg/kg dose group (a 53 percent increase in peak load for the
sclerostin antibody-treated group versus a vehicle-treated control
group). Peak load is one of several accepted measurements for
assessing bone strength.
Safety and efficacy data will become available once the clinical
development program is initiated.
Understanding the Needs, Lifestyles of Osteoporosis Patients
As part of Amgen's commitment to developing potential treatments
for osteoporosis, the company has initiated a large, comprehensive
multicenter study of 6,000 postmenopausal women in the U.S. and
Europe, entitled "Prospective Observational Scientific Study
Investigating Bone Loss Experience (POSSIBLE)." At the ASBMR meeting,
baseline data were presented from this study which was designed to
collect and analyze: the pattern of use of current osteoporosis
therapies; patient-attributed side-effect rates for these therapies;
patient-reported compliance rates; the associations among current
treatment and health-related quality of life, treatment satisfaction,
and resource utilization.
Denosumab is an investigational fully human monoclonal antibody
being studied for its potential to prevent and treat osteoporosis in
postmenopausal women. Denosumab is also being studied for its
potential in a broad range of bone loss conditions including bone
metastases, treatment-induced bone loss, multiple myeloma, and bone
erosions in rheumatoid arthritis.
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 three Phase 3 and two Phase 2 trials in
postmenopausal osteoporosis, Amgen is conducting a Phase 2 study in
the treatment of bone erosions in rheumatoid arthritis. 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 are evaluating
denosumab as a possible treatment for patients with multiple myeloma.
For more information about ongoing denosumab clinical trials,
please visit www.amgentrials.com or www.clinicaltrials.gov.
Often referred to as the "silent epidemic", osteoporosis is a
global problem which is increasing in significance as the population
of the world both grows and ages. The World Health Organization (WHO)
has recently identified osteoporosis as a priority health issue along
with other major non-communicable diseases.
Osteoporosis is a disease in which the density and quality of bone
are reduced, leading to weakness of the skeleton and increased risk of
fracture, particularly of the spine, wrist, hip, pelvis and upper arm.
Osteoporosis and associated fractures are an important cause of
mortality and morbidity.
More than 75 million people in Europe, Japan and the USA alone
suffer from osteoporosis, with an estimated lifetime risk for wrist,
hip and vertebral fractures of around 15 percent, very similar to that
of coronary heart disease.
Across the globe, the costs to healthcare systems from
osteoporosis-related hospitalization are significant. The annual
direct costs of treating osteoporosis fractures of people in the
workplace in the EU, Canada, and U.S. is approximately $48 billion per
year. In the U.S., costs are estimated at more than $30 billion; in
Europe, more than $17 billion; and in Canada, more than $1.9 billion.
Amgen discovers, develops 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 broad and deep 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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