Investigational Therapy Denosumab Increased Bone Mineral Density with Twice-Yearly Dosing; One Year Data Published in New England Journal of Medicine
THOUSAND OAKS, Calif., Feb 22, 2006 (BUSINESS WIRE) -- Amgen (NASDAQ: AMGN), the world's largest biotechnology
company, announced today the publication of Phase 2 data demonstrating
twice-yearly injections of denosumab (previously referred to as AMG
162), a RANK Ligand inhibitor, significantly increased bone mineral
density (BMD) in the total hip, lumbar spine, distal 1/3 radius and
total body compared to placebo. The results of this one-year study
appeared in the Feb. 23, 2006 issue of the New England Journal of
Medicine. Data results also included an open-label FOSAMAX(R)
(alendronate)(a) arm of the same clinical trial.
Researchers reported that subcutaneous injections of denosumab
significantly increased BMD at the total hip from 1.9 to 3.6 percent
in women who were administered the therapy twice yearly as compared
with a decrease of 0.6 percent in the placebo group (p less than
0.001) at one year. The open label FOSAMAX(R) group receiving 70 mg
weekly had an increase of 2.1 percent during the same time frame.
Results also indicated that denosumab had a rapid onset of action. A
significant decrease in serum levels of C-telopeptide, a biomarker of
bone resorption, was achieved within 72 hours after dosing.
"These exciting data suggest that denosumab, when administered in
twice-yearly injections, may show promise in the treatment of
osteoporosis," said Michael McClung, MD, FACP, principal investigator
of the denosumab study, Providence Portland Medical Center, and
director of the Oregon Osteoporosis Center, Portland, Ore. "Continued
research will further our understanding of the potential of denosumab
in bone loss management."
Denosumab targets RANK Ligand, a protein that acts as the primary
mediator of osteoclast (cells that break down bone) activity. This
investigational therapy is the first RANK Ligand inhibitor in late
Amgen is studying denosumab for its potential in a broad range of
conditions associated with bone destruction including osteoporosis,
treatment-induced bone loss, bone metastases, multiple myeloma and
rheumatoid arthritis. Data recently presented at the American College
of Rheumatology 2005 Annual Scientific Meeting show further increase
in bone mineral density in postmenopausal women with osteoporosis
after two years of treatment.
"These data reinforce the essential role that RANK Ligand
inhibition plays in decreasing bone loss," said Willard Dere, MD,
senior vice president of global development and chief medical officer,
Amgen. "We are committed to expanding our data on denosumab with an
extensive Phase 3 clinical program to evaluate the effect of denosumab
on preventing fractures in men and women."
In the one-year trial results, researchers also reported
twice-yearly subcutaneous injections of denosumab significantly
increased lumbar spine BMD from 3.0 to 6.7 percent after 12 months as
compared with a decrease of 0.8 percent in the placebo-treated
patients (p less than 0.001). Across all doses and dosing intervals,
distal 1/3 radius BMD increased from 0.4 to 1.3 percent as compared
with a decrease of 2.0 percent in those taking placebo (p less than
0.001), and total body BMD increased from 0.6 to 2.8 percent as
compared with a decrease of 0.2 percent in the placebo group (p less
The incidence of adverse events was similar among the denosumab,
placebo, and FOSAMAX(R) groups, with the exception of dyspepsia.
Dyspepsia occurred in 7 percent of placebo patients, 6-15 percent of
denosumab patients and 26 percent of open-label FOSAMAX(R) patients.
The most common adverse events among all groups included upper
respiratory infection (common cold), arthralgia (joint pain),
nasopharyngitis (sore throat), back pain and headache. No neutralizing
antibodies to denosumab were observed.
Denosumab Study Design
This is an ongoing, multi-center dose-ranging trial. Investigators
randomized 412 healthy postmenopausal women, average age 63, with low
BMD to receive denosumab, placebo or FOSAMAX(R). The purpose of the
study was to determine the safety and efficacy of denosumab on lumbar
spine BMD compared with placebo at 12 months. The doses of denosumab
evaluated included 6, 14 or 30 mg every three months or 14, 60, 100 or
210 mg every six months. The researchers administered all doses of
denosumab via subcutaneous injection. Patients receiving FOSAMAX(R)
followed the approved indication and oral dosing instructions of 70 mg
At entry, the average lumbar spine T score ranged from -2.0 to
-2.2 across dose groups, consistent with a diagnosis of osteopenia
(thinning bone). Approximately a quarter of the patients had
osteoporosis as defined by a T score equal to or below -2.5 at the
About RANK Ligand
Bone is constantly formed and removed through a natural process of
remodeling. Bone resorption is dependent on RANK Ligand, the protein
that acts as the primary mediator of osteoclast formation, function
and survival. Osteoclasts are cells responsible for bone removal.
Preclinical models have demonstrated that inhibiting RANK Ligand
significantly improves cortical and trabecular bone density, volume
and strength. Cortical bone is the protective outer shell around every
bone in the body. Trabecular bone is known as spongy bone and is
surrounded by the harder cortical layer.
The Need for Bone Loss Treatments
Bone loss represents a significant clinical and economic burden.
Osteoporosis is a major public health threat for an estimated 44
million Americans, or 55 percent of the population 50 years of age and
older. In the U.S. today, 10 million individuals are estimated to
already have the disease and almost 34 million more are estimated to
have low bone mass, placing them at increased risk for osteoporosis.
Of the 10 million Americans estimated to have osteoporosis, eight
million are women and two million are men. In addition, one in two
women and one in four men over age 50 will have an
osteoporosis-related fracture in their remaining lifetime.
In Europe, recent estimates have stated that approximately 3.8
million people have experienced bone fractures related to
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Nurha Hindi, 805-447-4587 (media)
Anthony Gringeri, PhD, 805-447-1060 (investors)