THOUSAND OAKS, Calif., Sept. 22 /PRNewswire-FirstCall/ -- Amgen
(NASDAQ: AMGN) today announced detailed results from a Phase 3,
head-to-head trial evaluating denosumab versus Zometa (zoledronic
acid) in the treatment of bone metastases in 2,046 patients with
advanced breast cancer that met its primary and secondary endpoints
and demonstrated superior efficacy compared to Zometa. These
results were presented today during the Presidential Session at the
2009 ECCO 15 - ESMO 34 European Multidisciplinary Congress in
Berlin, Germany (Abstract Number 2LBA). Denosumab administered
subcutaneously demonstrated superiority for both delaying the time
to the first on-study skeletal related events (SREs) (fracture,
radiation to bone, surgery to bone, or spinal cord compression)
(hazard ratio 0.82, 95 percent CI: 0.71, 0.95), and delaying the
time to first-and-subsequent SREs (hazard ratio 0.77, 95 percent
CI:0.66, 0.89). Both results were statistically significant in this
34 month study. The median time to first on-study SRE was not
reached for denosumab and therefore could not be estimated. The
median time to first on-study SRE was 26.5 months for Zometa, the
current standard of care. "Up to 80 percent of patients with
advanced breast cancer will develop bone metastases that are often
associated with severe and painful bone complications, which are a
serious concern for both patients and physicians," said Alison
Stopeck, M.D., associate professor of Medicine, Arizona Cancer
Center, University of Arizona Health Sciences Center, Tucson, AZ,
United States of America. "Denosumab was superior to Zometa in
preventing skeletal related events and delayed worsening of bone
pain. In addition, denosumab also presented some potential
tolerability advantages for many patients, including a lower
incidence of renal toxicity and acute phase reactions, combined
with the convenience of a monthly subcutaneous injection. Denosumab
would be a welcome new treatment option for advanced breast cancer
patients." Denosumab also delayed the median time to first on-study
SRE or hypercalcemia of malignancy (HCM) compared to Zometa (hazard
ratio 0.82, 95 percent CI: 0.70, 0.95; p=0.007). The median time to
first on-study SRE or HCM was not reached for denosumab and
therefore could not be estimated. The median time to first on-study
SRE or HCM was 25.2 months for Zometa. Bone pain can dominate the
daily lives of patients with metastatic disease involving bone and
is often characterized as severe or intolerable.(1) In a
pre-specified exploratory analysis, patients on the denosumab arm
reported worsening of pain later than those on the Zometa arm (88
days versus 64 days, respectively; hazard ratio 0.87, 95 percent
CI: 0.79, 0.97; p=0.009). Overall, the incidence of adverse events
(96 percent denosumab, 97 percent Zometa) and serious adverse
events (44 percent denosumab, 46 percent Zometa) was consistent
with what has previously been reported for these two agents.
Adverse events potentially associated with renal toxicity occurred
in 4.9 percent of patients treated with denosumab compared to 8.5
percent in patients treated with Zometa. Osteonecrosis of the jaw
(ONJ) was seen infrequently in both treatment groups (20 patients
receiving denosumab (2.0 percent) as compared with 14 patients (1.4
percent) receiving Zometa). There was no statistically significant
difference in the rate of ONJ between the two treatment arms.
Overall survival (hazard ratio 0.95, 95 percent CI: 0.81, 1.11;
p=0.50) and time to cancer progression (hazard ratio 0.99, 95
percent CI: 0.89, 1.11; p=0.90) was balanced between treatment
arms. Detailed data from another Phase 3, head-to-head trial
evaluating denosumab versus Zometa was presented yesterday
(Abstract #20LBA). In this study of 1,776 advanced cancer patients
with solid tumors (not including breast and prostate cancer) or
multiple myeloma, denosumab met its primary endpoint and
demonstrated non-inferiority compared to Zometa in the treatment of
bone metastases. Webcast Information An analyst/investor event will
also be held from the Congress on September 24th, at 6:30 a.m.
Eastern Time to discuss data presented at ECCO-ESMO. A webcast of
the event can be found on Amgen's Web site at
http://www.amgen.com/, under Investors. The audio webcast will be
archived and available for replay for at least 72 hours. Study
Design This was an international, Phase 3, randomized, double-blind
study comparing denosumab with Zometa in the treatment of bone
metastases in patients with advanced breast cancer. Patients
enrolled in the study were randomized in a one-to-one ratio to
receive either 120 mg of denosumab subcutaneously every four weeks
(Q4W) or Zometa administered intravenously at a dose of 4 mg in a
15 minute infusion every four weeks as per the label instructions.
In clinical trials testing new medications for bone metastases,
treatment success has been measured by whether the bone
complications, or SREs, caused by the tumor are reduced or delayed.
The primary and secondary endpoints of the denosumab bone
metastases studies use a composite endpoint of four SREs -
fracture, the need for radiation to bone, the need for bone
surgery, and spinal cord compression - to measure the effectiveness
of denosumab versus Zometa. The primary endpoint was to evaluate if
denosumab is non-inferior to Zometa with respect to the first,
on-study SRE in patients with advanced breast cancer and bone
metastases. Secondary endpoints were to evaluate if denosumab was
superior to Zometa with respect to the first, on-study SRE, as well
as the first-and-subsequent on-study SREs, and to assess the safety
and tolerability of denosumab compared with Zometa. About Denosumab
and Amgen's Research in Bone Biology Denosumab is the first fully
human monoclonal antibody in late stage clinical development that
specifically targets RANK Ligand, the essential regulator of
osteoclasts (the cells that break down bone). With more than 19,000
patients in trials across indications worldwide, the denosumab
development program is the largest ever initiated by Amgen. This
broad and deep development program demonstrates Amgen's commitment
to researching and delivering pioneering medicines to patients with
unmet medical needs. Amgen is studying denosumab in numerous tumor
types across the spectrum of cancer-induced bone disease. Over
11,000 patients have been enrolled in the denosumab oncology
clinical trials, testing the drug for the reduction of SREs in
breast cancer patients, for the amelioration of treatment-induced
bone loss in patients with breast or prostate cancers, for the
prevention of SREs due to the spread of cancer to the bone in
patients with multiple myeloma or those suffering from a variety of
solid tumors, and for its potential to delay bone metastases in
prostate cancer. Bone Metastases: Impact and Prevalence Bone
metastases, cancer cells that separate from tumors and migrate to
bone tissue where they settle and grow, occur in more than 1.5
million people worldwide.(2) With improvements in cancer care,
including earlier diagnosis and new treatment options, leading to
increases in survival rates(3), the number of patients developing
metastatic disease secondary to a primary cancer is increasing.
Bone metastases are a significant problem for patients with certain
types of advanced cancer, with incidence rates of nearly 100
percent in myeloma patients and as high as 75 percent in breast and
prostate cancer patients. With bone metastases the growing cancer
cells weaken and destroy the bone around the tumor. The damage the
tumor has caused to the bone can result in a number of serious
complications, collectively called SREs. These include fracture of
a bone, the need for radiation to bone, the need for bone surgery,
or spinal cord compression. All are serious complications for
advanced cancer patients. The economic burden of United States
(U.S.) patients with bone metastases is significant and was
estimated to be $12.6 billion last year.(4) Patients with bone
metastases who experience an SRE incur significantly higher medical
costs compared with those who do not experience an SRE.(5) About
Amgen 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 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
http://www.amgen.com/. Forward-Looking Statements This news release
contains forward-looking statements that are based on management's
current expectations and beliefs and are subject to a number of
risks, uncertainties and assumptions that could cause actual
results to differ materially from those described. All statements,
other than statements of historical fact, are statements that could
be deemed forward-looking statements, including estimates of
revenues, operating margins, capital expenditures, cash, other
financial metrics, expected legal, arbitration, political,
regulatory or clinical results or practices, customer and
prescriber patterns or practices, reimbursement activities and
outcomes and other such estimates and results. Forward-looking
statements involve significant risks and uncertainties, including
those discussed below and more fully described in the Securities
and Exchange Commission (SEC) reports filed by Amgen, including
Amgen's most recent annual report on Form 10-K and most recent
periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's
most recent Forms 10-K, 10-Q and 8-K for additional information on
the uncertainties and risk factors related to our business. Unless
otherwise noted, Amgen is providing this information as of Sept.
22, 2009 and expressly disclaims any duty to update information
contained in this news release. No forward-looking statement can be
guaranteed and actual results may differ materially from those we
project. Discovery or identification of new product candidates or
development of new indications for existing products cannot be
guaranteed and movement from concept to product is uncertain;
consequently, there can be no guarantee that any particular product
candidate or development of a new indication for an existing
product will be successful and become a commercial product.
Further, preclinical results do not guarantee safe and effective
performance of product candidates in humans. The complexity of the
human body cannot be perfectly, or sometimes, even adequately
modeled by computer or cell culture systems or animal models. The
length of time that it takes for us to complete clinical trials and
obtain regulatory approval for product marketing has in the past
varied and we expect similar variability in the future. We develop
product candidates internally and through licensing collaborations,
partnerships and joint ventures. Product candidates that are
derived from relationships may be subject to disputes between the
parties or may prove to be not as effective or as safe as we may
have believed at the time of entering into such relationship. Also,
we or others could identify safety, side effects or manufacturing
problems with our products after they are on the market. Our
business may be impacted by government investigations, litigation
and products liability claims. We depend on third parties for a
significant portion of our manufacturing capacity for the supply of
certain of our current and future products and limits on supply may
constrain sales of certain of our current products and product
candidate development. In addition, sales of our products are
affected by the reimbursement policies imposed by third-party
payors, including governments, private insurance plans and managed
care providers and may be affected by regulatory, clinical and
guideline developments and domestic and international trends toward
managed care and health care cost containment as well as U.S.
legislation affecting pharmaceutical pricing and reimbursement.
Government and others' regulations and reimbursement policies may
affect the development, usage and pricing of our products. In
addition, we compete with other companies with respect to some of
our marketed products as well as for the discovery and development
of new products. We believe that some of our newer products,
product candidates or new indications for existing products, may
face competition when and as they are approved and marketed. Our
products may compete against products that have lower prices,
established reimbursement, superior performance, are easier to
administer, or that are otherwise competitive with our products. In
addition, while we routinely obtain patents for our products and
technology, the protection offered by our patents and patent
applications may be challenged, invalidated or circumvented by our
competitors and there can be no guarantee of our ability to obtain
or maintain patent protection for our products or product
candidates. We cannot guarantee that we will be able to produce
commercially successful products or maintain the commercial success
of our existing products. Our stock price may be affected by actual
or perceived market opportunity, competitive position, and success
or failure of our products or product candidates. Further, the
discovery of significant problems with a product similar to one of
our products that implicate an entire class of products could have
a material adverse effect on sales of the affected products and on
our business and results of operations. The scientific information
discussed in this news release relating to new indications for our
products is preliminary and investigative and is not part of the
labeling approved by the U.S. Food and Drug Administration (FDA)
for the products. The products are not approved for the
investigational use(s) discussed in this news release, and no
conclusions can or should be drawn regarding the safety or
effectiveness of the products for these uses. Only the FDA can
determine whether the products are safe and effective for these
uses. Healthcare professionals should refer to and rely upon the
FDA-approved labeling for the products, and not the information
discussed in this news release. ZOMETA is a registered trademark of
Novartis Oncology. *Editors Note: The FDA has provisionally
approved the trade name Prolia(TM) for the proposed indications of
treatment and prevention of osteoporosis in postmenopausal women,
and treatment and prevention of bone loss in patients undergoing
hormone ablation for non-metastatic prostate or breast cancer, for
which denosumab is administered twice yearly subcutaneously at a 60
mg dose. The Prolia(TM) trade name is only for these indications
and may not apply for other indications of denosumab. (1) Diel IJ.
Effectiveness of bisphosphonates on bone pain and quality of life
in breast cancer patients with metastatic bone disease: A review.
Support Care Cancer. 2007: 15:1243-1249. (2) Coleman, R. Potential
use of bisphosphonates in the prevention of metastases in
early-stage breast cancer. Clin Breast Cancer. 2007; 7(Suppl
1):S29-35. 2Coleman RE. Metastatic bone disease: clinical features,
pathophysiology and treatment strategies. Cancer Treat Rev.
2001;27:165-76. (3) Capanna R, Coia LR, Coleman R. et al. eds.
Textbook of Bone Metastases. Hoboken, NJ: Edition: John Wiley and
Sons; 2005:105. (4) Mundy GR. Metastasis to bone: causes,
consequences and therapeutic opportunities. Nat Rev Cancer. 2002
Aug;2(8):584-93. (5) Schulman K and Kohles J. Cancer.
2007;109:2334-2342 (6) GVD/Barber ISPOR 2008 Poster; Schulman 2007;
Delea et al. 2006 CONTACT: Amgen, Thousand Oaks Sabeena Ahmad: +41
(0) 41-369-2530 (media Europe/Australia) Lisa Rooney: +1 (805)
447-6437 (media U.S.) Arvind Sood: +1 (805) 447-1060 (investors)
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http://photoarchive.ap.org/ DATASOURCE: Amgen CONTACT: media
Europe/Australia, Sabeena Ahmad, +41 (0) 41-369-2530, or media
U.S., Lisa Rooney, +1-805-447-6437, or investors, Arvind Sood,
+1-805-447-1060, all of Amgen, Thousand Oaks Web Site:
http://www.amgen.com/
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