THOUSAND OAKS, Calif., Sept. 21 /PRNewswire-FirstCall/ -- Amgen
(NASDAQ: AMGN) today announced detailed results from a Phase 3
trial evaluating denosumab administered subcutaneously versus
Zometa (zoledronic acid) administered as an intravenous infusion in
the treatment of bone metastases in 1,776 advanced cancer patients
with solid tumors (not including breast and prostate cancer) or
multiple myeloma. These results were presented today at the 2009
ECCO 15 - ESMO 34 European Multidisciplinary Congress in Berlin,
Germany (Abstract Number: 20LBA). For the primary endpoint of this
study, the median time to first on-study skeletal related event
(SRE) (fracture, radiation to bone, surgery to bone, or spinal cord
compression) was 20.6 months for those patients receiving denosumab
and 16.3 months for those patients receiving Zometa (hazard ratio
0.84, 95 percent CI: 0.71-0.98), which is statistically significant
for non-inferiority (p=0.0007). Although numerically greater, the
delay in the time to first SRE associated with denosumab was not
statistically superior compared to Zometa based upon the
statistical testing strategy (adjusted p=0.06) (secondary
endpoint). The time to first-and-subsequent SRE was also
numerically greater but not statistically superior compared to
Zometa (hazard ratio 0.90, 95 percent CI: 0.77-1.04, p=0.14)
(secondary endpoint). "It is encouraging to see denosumab's
efficacy in this broad cancer population. There is no need for
renal monitoring or dose adjustments due to renal impairment," said
David Henry, M.D., clinical professor of Medicine, Pennsylvania
Hospital, Philadelphia, PA, United States of America. "Furthermore,
the positive results of this study, combined with the convenience
of a monthly subcutaneous injection and without the flu-like
symptoms associated with Zometa administration, make this an
exciting potential treatment option for advanced cancer patients."
Bone metastases, the spread of tumors to the bone, are a serious
concern for many advanced cancer patients. When cancer spreads to
the bone, the growing cancer cells weaken and destroy the bone
around the tumor. This damage can result in a number of serious
bone complications, collectively called skeletal related events.
Denosumab also delayed the median time to first on-study SRE or
hypercalcemia of malignancy (HCM) compared to Zometa (hazard ratio
0.83, 95 percent CI: 0.71, 0.97; p=0.02). The median time to first
on-study SRE or HCM was 19.0 months for denosumab and 14.4 months
for Zometa. Bone destruction is a major cause of pain in
approximately 70 percent of patients with metastatic disease. (1)
In an exploratory analysis, patients on the denosumab arm reported
worsening of pain later than those on the Zometa arm (57 days
versus 36 days, respectively). Adverse events rates (96 percent
denosumab, 96 percent Zometa) and serious adverse events (63
percent denosumab, 66 percent Zometa) were similar between groups
and were consistent with what has previously been reported for
these two agents. Rates of osteonecrosis of the jaw (ONJ) were
balanced and infrequent in both treatment groups (10 patients
receiving denosumab as compared with 11 patients receiving Zometa).
Infectious adverse events were balanced between the two treatment
arms, as was overall survival (hazard ratio 0.95, 95 percent CI:
0.83-1.08; p=0.43) and the time to cancer progression (hazard ratio
1.00, 95 percent CI: 0.89, 1.12; p=1.0). Detailed data from a
second Phase 3, head-to-head trial evaluating denosumab versus
Zometa will be presented Tuesday, Sept. 22, 2009 at 14:15 - 14:30
Central European Summer Time (CEST) in the Presidential Session of
ECCO-ESMO (Abstract #2LBA; presentation embargoed until 12:15 CEST
Sept. 22, 2009). In this study of 2,049 patients with advanced
breast cancer, denosumab met all primary and secondary endpoints
and demonstrated superior efficacy compared to Zometa in the
treatment of bone metastases. Webcast Information Denosumab data
presented at ECCO-ESMO today will be discussed by Roger M.
Perlmutter, M.D., Ph.D., executive vice president of Research and
Development at Amgen at the UBS Global Life Sciences Conference in
New York this morning at 8:30 a.m. Eastern Time (ET). Live audio of
the presentation will be available over the Internet and can be
accessed from Amgen's Web site at http://www.amgen.com/, under
Investors. An analyst/investor event will also be held from the
Congress on September 24th, at 6:30 a.m. ET 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, active-comparator-controlled study
comparing denosumab with Zometa in the treatment of bone metastases
in patients with advanced cancer (excluding breast and prostate
cancer) or multiple myeloma. Patients enrolled in this event-driven
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 delivered as a single,
15-minute infusion every four weeks. In clinical trials thus far to
test 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 cancer
(excluding breast and prostate cancer) or multiple myeloma and bone
metastases. Secondary endpoints were to evaluate if denosumab is
superior to Zometa with respect to the first on-study SRE, as well
as 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 solid
tumor 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. Regardless of the type of underlying
cancer, the process by which cancers invade and destroy bones is
fundamentally the same. At the center of this destructive process
is a protein RANK Ligand that is stimulated by the presence of
cancer in the bone. The economic burden of 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.
21, 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. CONTACT:
Amgen, Thousand Oaks Sabeena Ahmad: +41 (0) 41 369 25 30 (media
Europe/Australia) Lisa Rooney: +1 (805) 447-6437 (media U.S.)
Arvind Sood: +1 (805) 447-1060 (investors) (Logo:
http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO) 1. Cleeland
CS, et al. Pain and its treatment in outpatients with metastatic
cancer. N Engl J Med. 1994: 330:592-596. 2. Capanna R, Coia LR,
Coleman R. et al. eds. Textbook of Bone Metastases. Hoboken, NJ:
Edition: John Wiley and Sons; 2005:105. 3. Mundy GR. Metastasis to
bone: causes, consequences and therapeutic opportunities. Nat Rev
Cancer. 2002 Aug;2(8):584-93. 4. Schulman K and Kohles J. Cancer.
2007;109:2334-2342 5. GVD/Barber ISPOR 2008 Poster; Schulman 2007;
Delea et al. 2006
http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO
http://photoarchive.ap.org/ DATASOURCE: Amgen CONTACT: media
Europe/Australia, Sabeena Ahmad, +41 (0) 41 369 25 30, 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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