THOUSAND OAKS, Calif., Sept. 24 /PRNewswire-FirstCall/ -- Amgen
(NASDAQ: AMGN) today announced detailed results from the Phase 3
'203' trial evaluating Vectibix (panitumumab) administered in
combination with FOLFOX (an oxaliplatin-based chemotherapy) as the
first-line treatment of metastatic colorectal cancer (mCRC). In
this trial, Vectibix significantly improved median progression-free
survival (PFS) by 1.6 months (9.6 versus 8.0 months for patients
treated with FOLFOX alone, (hazard ratio 0.80; p=0.02)) in patients
with KRAS wild-type mCRC (primary endpoint). The results were
presented at the 2009 ECCO 15 - ESMO 34 European Multidisciplinary
Congress in Berlin, Germany (Abstract Number 10LBA). Further, the
addition of Vectibix to chemotherapy also improved response rate in
the KRAS wild-type patient population as measured by blinded
central review (55 percent versus 48 percent in the FOLFOX only
arm). "I am very pleased with the outcome of this high quality
trial which demonstrated that Vectibix improved progression-free
survival and appeared to be well tolerated as a first-line
metastatic colorectal cancer treatment in a selected patient
population," said Jean-Yves Douillard, director Clinical and
Translational Research, Medical Oncology Branch, Centre R
Gauducheau, France and the study's principal investigator. "This is
the first prospective Phase 3 data to demonstrate the importance of
KRAS mutation as a predictive biomarker for Vectibix treatment in
the first-line setting, providing definitive support for the use of
the KRAS biomarker for selection of patients eligible for anti-EGFR
therapy." Importantly, in patients with tumors harboring activating
KRAS mutations, PFS was significantly inferior in the Vectibix arm.
For patients with mutant KRAS tumors, median PFS was 7.3 months
with Vectibix in combination with FOLFOX vs. 8.8 months with FOLFOX
alone (hazard ratio 1.29, p=0.02). These data confirm previous
findings when oxaliplatin-based chemotherapy and an anti-epidermal
growth factor receptor (EGFR) antibody are combined in patients
bearing tumors with activating KRAS mutations. Consistent with the
PFS data, an interim analysis of overall survival, a secondary
endpoint, demonstrated a reduction in overall survival in patients
with KRAS mutant tumors receiving Vectibix. The median overall
survival for patients with KRAS wild-type mCRC has not yet been
reached. Long-term follow-up for survival continues and the primary
analysis is expected in the fourth quarter of 2009. Adverse event
rates were comparable across arms with the exception of known
toxicities associated with anti-epidermal growth factor receptor
(EGFR) therapy such as rash, diarrhea and hypomagnesemia.
Vectibix-related grade 3 infusion reactions were reported for two
patients (less than 1 percent). Originally designed to compare the
treatment effect in the overall population, the study was amended
to analyze outcomes with respect to the presence or absence of
activating mutations in KRAS in the tumor itself. Tumor KRAS status
was ascertained in 93 percent of the 1,183 patients enrolled in the
trial, the highest percentage ever reported. Tumor KRAS tests were
finalized after the completion of enrollment and prior to the
primary analysis. Earlier this week, data were presented from the
'181' trial which showed that Vectibix administered in combination
with FOLFIRI (an irinotecan-based chemotherapy) prolonged PFS by 2
months in patients with KRAS wild-type mCRC, compared to treatment
with FOLFIRI alone (Abstract Number 14LBA). 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 Patients enrolled in the '203' or PRIME trial
(Panitumumab Randomized trial In combination with chemotherapy for
Metastatic colorectal cancer to determine Efficacy) were randomized
to receive either 6.0 mg/kg of Vectibix and FOLFOX4 once every two
weeks (Q2W) or FOLFOX4 alone Q2W. The primary endpoint of the study
is progression-free survival by KRAS status and secondary endpoints
include overall survival, objective response rate, time to
progression, duration of response and safety. Long-term follow up
for overall survival is ongoing. About KRAS Results from studies
performed over the last twenty-five years indicate that KRAS plays
an important role in cell growth regulation. In mCRC, EGFR
transmits signals through a set of intracellular proteins. Upon
reaching the nucleus, these signals instruct the cancer cell to
reproduce and metastasize, leading to cancer progression. Anti-EGFR
antibody therapies work by blocking the activation of EGFR, thereby
inhibiting downstream events that lead to malignant signaling.
However, it is hypothesized that in patients whose tumors harbor a
mutated KRAS gene, the KRAS protein is always turned "on,"
regardless of whether the EGFR has been activated or
therapeutically inhibited. KRAS mutations occur in approximately
40-50 percent of mCRC. About Colorectal Cancer Colorectal cancer is
the fourth most common cancer in men and the third most common
cancer in women worldwide. In 2007, approximately 1.2 million cases
of colorectal cancer were expected to occur globally. With more
than 630,000 deaths worldwide per year, it is the second leading
cause of cancer-related death in the Western world. The highest
incidence rates are found in Japan, North America, parts of Europe,
New Zealand, and Australia, and rates are low in Africa and
South-East Asia. Rates are substantially higher in men than in
women. About Vectibix Vectibix is the first fully human anti-EGFR
antibody approved by the U.S. Food and Drug Administration (FDA)
for the treatment of mCRC. Vectibix was approved in the United
States in September 2006 as a monotherapy for the treatment of
patients with EGFR expressing mCRC after disease progression on or
following fluoropyrimidine-, oxaliplatin-, and
irinotecan-containing chemotherapy regimens. The effectiveness of
Vectibix as a single agent for the treatment of EGFR-expressing,
metastatic colorectal carcinoma is based on progression-free
survival. Currently no data are available that demonstrate an
improvement in disease-related symptoms or increased survival with
Vectibix. Vectibix has not shown a treatment benefit for patients
whose tumors had KRAS mutations in codon 12 or 13. In December
2007, the EMEA granted a conditional marketing authorization for
Vectibix as monotherapy for the treatment of patients with
EGFR-expressing mCRC with wild-type KRAS genes after failure of
standard chemotherapy regimens. Vectibix has been launched in over
20 countries, Switzerland, Australia and Canada. Applications in
the rest of the world, including Japan, are pending. Important
Product Safety Information Dermatologic Toxicity: Dermatologic
toxicities occurred in 89 percent of patients and were severe
(NCI-CTC grade 3 and higher) in 12 percent of patients receiving
Vectibix monotherapy. Withhold Vectibix for dermatologic toxicities
that are grade 3 or higher or are considered intolerable. If
toxicity does not improve to greater than or equal to grade 2
within 1 month, permanently discontinue Vectibix. The clinical
manifestations included, but were not limited to, dermatitis
acneiform, pruritus, erythema, rash, skin exfoliation, paronychia,
dry skin, and skin fissures. Subsequent to the development of
severe dermatologic toxicities, infectious complications, including
sepsis, septic death, and abscesses requiring incisions and
drainage were reported. Infusion Reactions: Severe infusion
reactions occurred in approximately 1 percent of patients. Severe
infusion reactions included anaphylactic reactions, bronchospasm,
and hypotension. Although not reported with Vectibix, fatal
infusion reactions have occurred with other monoclonal antibody
products. Stop infusion if a severe infusion reaction occurs.
Depending on the severity and/or persistence of the reaction,
permanently discontinue Vectibix. About Amgen Amgen discovers,
develops, manufactures 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
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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. 24, 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
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entering into such relationship. Also, we or others could identify
safety, side effects or manufacturing problems with our products
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care cost containment as well as U.S. legislation affecting
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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
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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
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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. CONTACT: Amgen, Thousand Oaks
Christine Regan: 805-447-5476 (media U.S.) Wendy Woods: +41 (0) 41
3692 542 (media Europe) Arvind Sood: 805-447-1060 (investors)
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