New Analyses Identify Predictive Biomarkers For Vectibix® (Panitumumab) In Patients With Metastatic Colorectal Cancer

  New Analyses Identify Predictive Biomarkers For Vectibix® (Panitumumab) In
                  Patients With Metastatic Colorectal Cancer

Biomarker Analysis From Phase 3 PRIME ('203) Study and Phase 2 PEAK ('509)
Study Link Additional RAS Gene Mutations to Vectibix Clinical Response

PR Newswire

THOUSAND OAKS, Calif., May 15, 2013

THOUSAND OAKS, Calif., May 15, 2013 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced results from three analyses of Vectibix^® (panitumumab) in
combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, as a
first-line treatment for metastatic colorectal cancer (mCRC). These analyses
include the description of new predictive biomarkers of clinical response to
Vectibix, activating mutations in KRAS (beyond exon 2) and mutations in NRAS,
collectively referred to as RAS.

"Amgen helped establish KRAS gene mutation as a biomarker for lack of response
to anti-EGFR treatment," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "The identification of new biomarkers
may further help to identify appropriate patients with this incurable disease
for such treatment."

The RAS biomarkers were identified in a predefined retrospective subset
analysis of the PRIME trial, where RAS was defined as exons 2, 3 and 4 of KRAS
and NRAS. Mutational status of tumors was determined by Sanger sequencing in
parallel with WAVE®-based SURVEYOR® Scan Kits (CRC RAScan™) from Transgenomic,
Inc. (TBIO). In this exploratory analysis, patients with wild-type RAS mCRC
who were administered Vectibix in combination with FOLFOX demonstrated an
improvement in median overall survival (OS) of 26.0 months compared to 20.2
months for patients treated with FOLFOX alone (HR = 0.78, 95 percent CI,
0.62-0.99).

Patients with mutant RAS tumor status had inferior progression-free survival
(PFS) (HR = 1.34, 95 percent CI, 1.07-1.60) and OS (HR = 1.25, 95 percent CI,
1.02-1.55) when administered Vectibix in combination with FOLFOX chemotherapy
versus FOLFOX alone. These results suggest that RAS mutation status beyond
KRAS may be predictive of negative outcomes in patients receiving Vectibix
plus FOLFOX in mCRC. Amgen is working to inform investigators and physicians
of this important new safety information, as well as working with regulatory
agencies regarding appropriate communication of the outcomes of this analysis.

Results of this study will be presented at the 2013 American Society of
Clinical Oncology (ASCO) Annual Meeting on Tuesday, June 4, 8:00 a.m. - 12:00
p.m. CDT, S405 (Abstract No. 3511; Poster Discussion).

In a separate and updated exploratory analysis of longer follow-up of OS of
the PRIME trial (primary endpoint of PFS), an improvement in OS was observed
in patients with wild-type KRAS exon 2 mCRC treated with Vectibix in
combination with FOLFOX. Median OS was 23.8 months compared to 19.4 months for
patients treated with FOLFOX alone (HR = 0.83, 95 percent CI, 0.70-0.98). In
both PRIME analyses, the most commonly reported adverse events for the
Vectibix treatment arms included rash, hypomagnesemia and diarrhea. The
adverse event profiles for the wild-type tumor and mutant tumor populations
were similar.

Updated results of the study will be presented at the 2013 ASCO Annual Meeting
on Sunday, June 2, 8:00 a.m. - 11:45 a.m. CDT, S Hall A2 (Abstract No. 3620;
Poster).

In a separate predefined secondary objective subset analysis of the PEAK
study, patients with wild-type RAS mCRC treated with Vectibix in combination
with FOLFOX had a median PFS of 13.1 months compared to 9.5 months (HR = 0.63,
95 percent CI, 0.43-0.94) for patients treated with bevacizumab in combination
with FOLFOX. Median OS was not reached in the Vectibix arm, but the OS HR
favored the Vectibix arm (HR = 0.55, 95 percent CI, 0.33-1.01). The most
commonly reported adverse events for the Vectibix treatment arm included rash,
hypomagnesemia and dehydration. The adverse event profiles for the wild-type
tumor and mutant tumor populations were similar. No new toxicities were
identified for Vectibix.

Updated results of the study will be presented at the 2013 ASCO Annual Meeting
on Sunday, June 2, 8:00 a.m. - 11:45 a.m. CDT, S Hall A2 (Abstract No. 3631;
Poster).

PRIME ('203) Study Design
The PRIME (Panitumumab Randomized trial In combination with chemotherapy for
Metastatic colorectal cancer to determine Efficacy) ('203) trial is a global,
multicenter, randomized Phase 3 study designed to evaluate (primary endpoint
of PFS) Vectibix (6.0 mg/kg every two weeks) plus FOLFOX versus FOLFOX alone
in patients with wild-type KRAS exon 2 mCRC. The primary objective of this
predefined retrospective subset analysis was to determine the effect of
Vectibix plus FOLFOX versus FOLFOX alone on overall survival in patients with
mCRC based on RAS or BRAF mutation status. A total of 641 patients were
included in this analysis. RAS status was ascertained in 90 percent of the
patients with wild-type KRAS tumors.

PEAK ('509) Study Design
The PEAK (Panitumumab Efficacy in Combination with mFOLFOX6 Against
bevacizumab plus mFOLFOX6 in mCRC subjects with wild-type KRAS tumors) ('509)
trial is a global, multicenter, randomized Phase 2 study designed to compare
the efficacy (primary endpoint of PFS) of Vectibix in combination with FOLFOX
to the efficacy of bevacizumab in combination with FOLFOX in patients with
previously untreated, unresectable, wild-type KRAS exon 2 mCRC. The primary
objective of this predefined retrospective subset analysis was to determine
the effect of Vectibix plus FOLFOX versus bevacizumab plus FOLFOX on PFS and
OS in patients with mCRC based on RAS mutation status.

About KRAS and RAS
Results from studies performed over the last 25 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.^1 Anti-EGFR antibody therapies work by inhibiting the
activation of EGFR, thereby inhibiting downstream events that lead to
malignant signaling. However, 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. Common KRAS mutations
occurring in exon 2 (codons 12/13) are present in approximately 40 to 50
percent of mCRC patients.^2,3 RAS mutations are mutations occurring in exons
2, 3 and 4 of KRAS and NRAS and based on study data, appear to occur in
approximately 16 percent of patients with wild-type KRAS exon 2.

About Colorectal Cancer
Colorectal cancer is the third most common cancer found in both men and women
in the United States, and is the second leading cause of cancer deaths.^4,5
Approximately 1.2 million people are living with colorectal cancer globally.
The highest incidence rates are found in Japan, North America, parts of
Europe, New Zealand and Australia, and rates are low in Africa and Southeast
Asia.^6

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 single agent for the treatment of
patients with EGFR-expressing mCRC with 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 mCRC is based on PFS. More than half of patients who receive
Vectibix monotherapy respond to treatment with an average six month PFS
benefit. Currently, no data are available that demonstrate an improvement in
disease-related symptoms or increased survival with Vectibix.

Retrospective subset analyses of mCRC trials have not shown a treatment
benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12
or 13. Use of Vectibix is not recommended for the treatment of mCRC with these
mutations.^7

Important U.S. Product Information
Vectibix is indicated as a single agent for the treatment of EGFR-expressing
mCRC with 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 mCRC is based on
progression-free survival. Currently, no data demonstrate an improvement in
disease-related symptoms or increased survival with Vectibix.

Vectibix is not indicated for the treatment of patients with KRAS
mutation-positive mCRC or for whom KRAS mCRC status is unknown. Retrospective
subset analyses of metastatic colorectal cancer trials have not shown a
treatment benefit for Vectibix in patients whose tumors had KRAS mutations in
codon 12 or 13.

WARNING: DERMATOLOGIC TOXICITY and INFUSION REACTIONS
Dermatologic Toxicity: Dermatologic toxicities occurred in 89 percent of
patients and were severe (NCI-CTC grade 3 or higher) in 12 percent of patients
receiving Vectibix monotherapy. [See Dosage and Administration (2.1), Warnings
and Precautions (5.1), and Adverse Reactions (6.1)].

Infusion Reactions: Severe infusion reactions occurred in approximately one
percent of patients. Fatal infusion reactions occurred in postmarketing
experience [See Dosage and Administration (2.1), Warnings and Precautions
(5.2), and Adverse Reactions (6.1, 6.3)].

The most common adverse events of Vectibix are skin rash with variable
presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea and
diarrhea, including diarrhea resulting in dehydration.

The most serious adverse reactions of Vectibix are pulmonary fibrosis,
pulmonary embolism, severe dermatologic toxicity complicated by infectious
sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia,
nausea, vomiting and constipation.

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, effective
medicines from lab to manufacturing plant to patient. Amgen therapeutics have
changed the practice of medicine, helping people around the world in the fight
against serious illnesses. With a deep and broad pipeline of potential new
medicines, Amgen remains committed to advancing science to dramatically
improve people's lives. For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.

Forward-Looking Statements
This news release contains forward-looking statements that are based on
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CONTACT: Amgen, Thousand Oaks
Ashleigh Koss, 805-313-6151 (media)
Arvind Sood, 805-447-1060 (investors)

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^1 Malumbres, M. and Barbacid, M. RAS oncogenes: the first 30 years. Nature Reviews Cancer.  3:459-65,
   2003.
^2 Karapentis C, S. Snell, L, E. The Laboratory Assessment of KRAS Mutation Status in  Colorectal
   Cancer. Asia Pacific Journal of Oncology and Hematology. 2010.
^3 Friday BB and Adjei AA. K-ras as a target for cancer therapy. Biochim. Biophys. Acta 1756: 
   127-144, 2005.
   Cancer Facts and Figures 2013. American Cancer Society website. 
^4 http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf.
   Accessed March 25, 2013.
^5 Colorectal Cancer Prevention (PDQ^®). National Cancer Institute. Accessed March 25, 2013. 
   http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page3.
^6 Jemal. Global Cancer Statistics. CA Cancer J Clin. 2011;61:69-90.
^7 Vectibix (panitumumab) Prescribing Information. Thousand Oaks, Calif: Amgen; 2011.

SOURCE Amgen

Website: http://www.amgen.com