Phase 3 Trial Shows Denosumab Delayed Skeletal Related Events in Advanced Cancer Patients With Bone Metastases

Thousand Oaks, California (ots/PRNewswire) -

Amgen (Nasdaq: AMGN) today announced detailed results from a
Phase 3 trial evaluating denosumab administered subcutaneously versus
Zometa(R) (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 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
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 US$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 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

ots Originaltext: Amgen Inc.
Im Internet recherchierbar: http://www.presseportal.de

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 / Photo:
http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO