Denosumab Demonstrates Superiority Over Zometa(R) in Delay of Complications Due to Bone Metastases in Advanced Breast Cancer Patients

Thousand Oaks, California (ots/PRNewswire) -

Amgen (Nasdaq: AMGN) today announced detailed results from a
Phase 3, head-to-head trial evaluating denosumab versus Zometa(R)
(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 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 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.

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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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