Amgen Receives Positive CHMP Opinion for Vectibix® (Panitumumab) in Combination With Chemotherapy

Thousand Oaks, California (ots/PRNewswire) -

Amgen today announced that the Committee for Medicinal Products
for Human Use (CHMP) of the European Medicines Agency (EMA) has
adopted a positive opinion recommending that Vectibix(R)
(panitumumab) be approved for use in the European Union (EU) in
first-line in combination with FOLFOX and in second-line in
combination with FOLFIRI in patients who have received first-line
fluoropyrimidine-based chemotherapy (excluding irinotecan) for
patients with wild-type KRAS metastatic colorectal cancer (mCRC),
following a successful re-examination procedure by Amgen.

"This opinion, for which a final European Commission decision is
pending, is a welcome step forward and one that may lead to
additional treatment options for patients facing an aggressive
disease with limited treatment options," said Willard H. Dere, M.D.,
senior vice president and international chief medical officer at
Amgen. "Studies have shown that patients taking Vectibix in
combination with chemotherapy have a greater chance of living longer
without their disease getting worse, in a landscape where few
targeted agents have been shown to be effective when used with
chemotherapy."

Data from studies 20050203 (PRIME) and 20050181 ('181) showed
that adding Vectibix to either FOLFOX or FOLFIRI chemotherapy
improved progression-free survival (PFS) versus chemotherapy alone
for patients with wild-type KRAS mCRC. Additionally, the overall
response rate (ORR) of Vectibix plus chemotherapy was higher than
chemotherapy alone. Although numerically greater, the improvement in
median overall survival (OS) did not achieve statistical significance
in the Vectibix arm of either trial.(i)

The PRIME study evaluated Vectibix (6.0 mg/kg every two weeks)
plus FOLFOX versus FOLFOX alone in patients with wild-type KRAS mCRC
and found that Vectibix plus FOLFOX significantly improved PFS versus
FOLFOX alone (median 9.6 months versus 8.0 months, hazard ratio (HR)
0.80; 95 percent confidence interval (CI): 0.66-0.97; p=0.02).(i)
Additionally, combining Vectibix with FOLFOX resulted in numerically
greater OS versus FOLFOX alone (median 23.9 months versus 19.7
months, HR 0.83; 95 percent CI: 0.67-1.02), although this was not
statistically significant (p=0.072).(i) The ORR achieved with
Vectibix plus FOLFOX was higher than FOLFOX alone (55 percent versus
48 percent).(i)

The '181 study showed that adding Vectibix (6.0 mg/kg every two
weeks) to FOLFIRI chemotherapy improved median PFS by two months in
patients with wild-type KRAS mCRC compared to FOLFIRI alone (median
5.9 months versus 3.9 months; HR 0.73, 95 percent CI: 0.59-0.90;
p=0.004). Additionally, the Vectibix combination more than tripled
the ORR compared to FOLFIRI alone (35 percent versus 10 percent).
Though quantitatively greater (14.5 months versus 12.5 months, HR
0.85), the improvement in median OS (co-primary endpoint) did not
achieve statistical significance in the Vectibix arm of the trial
(p=0.12).(ii)

Adverse event rates included known toxicities associated with
anti-epidermal growth factor receptor (EGFR) therapy, such as rash,
diarrhea, and hypomagnesemia. Vectibix-related grade 3/4 infusion
reactions were reported in less than one percent of patients.(i) In
patients with mutated KRAS tumors, outcomes were inferior for those
receiving Vectibix plus FOLFOX versus FOLFOX alone.(ii iii) Vectibix
should only be used in those patients in whom wild-type KRAS status
has been confirmed, because of the worse outcomes in patients with
mutated KRAS tumors treated with FOLFOX.

The Amgen PRIME and '181 studies were the first Phase 3 studies
to prospectively analyze the effect of an EGFR inhibitor based on
KRAS status in patients with mCRC.

Vectibix is already approved and established in 40 countries as a
monotherapy treatment for patients with wild-type KRAS mCRC, when
standard chemotherapy is no longer effective. In the United States
(U.S.), Vectibix received accelerated approval 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
use of Vectibix is not recommended in patients whose tumors have KRAS
mutations in codon 12 or 13. In Japan and Israel, Vectibix is also
approved for use in combination with chemotherapy for patients with
wild-type KRAS mCRC.

About KRAS

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.(iv)
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. KRAS
mutations occur in approximately 40 to 50 percent of mCRC patients.(v
vi)

About Colorectal Cancer

Colorectal cancer is the third most common cancer worldwide in
men and the second most common in women. In 2008, approximately 1.23
million cases of colorectal cancer were diagnosed globally.(vii) In
2008, there were an estimated 333,330 new cases of colorectal cancer
in the EU.(viii)

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 U.S. 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 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.(ix)

In December 2007, the European Commission granted a conditional
marketing authorization for Vectibix as a monotherapy for the
treatment of patients with EGFR-expressing mCRC with non-mutated
(wild-type) KRAS after failure of fluoropyrimidine-, oxaliplatin-,
and irinotecan-containing chemotherapy regimens.(x) Vectibix has been
launched in more than 30 European countries, Russia, Israel,
Australia, Canada and Japan. Applications in the rest of the world
are pending.

Important U.S. Product Safety Information

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.

Important European Product Safety Information

For full prescribing information please see the Summary of
Product Characteristics.

Vectibix is indicated as monotherapy for the treatment of
patients with EGFR-expressing, mCRC with nonmutated (wild-type) KRAS
after failure of fluoropyrimidine-, oxaliplatin-, and
irinotecan-containing chemotherapy regimens.

Vectibix is contraindicated in patients with a history of severe
or life-threatening hypersensitivity reactions to the product and in
patients with interstitial pneumonitis or pulmonary fibrosis.

Other common adverse events of special importance associated with
Vectibix and/or EGFR monoclonal antibody therapies include
dermatologic-related reactions, pulmonary complications, electrolyte
disturbances and infusion-related reactions (including rare reports
with fatal outcome). These events should be monitored carefully, see
Summary of Product Characteristics for information on appropriate
management of these adverse events. Acute renal failure has been
observed in patients who develop severe diarrhoea and dehydration.

Vectibix should not be used in combination with IFL [bolus
5-fluorouracil (500 mg/m2), leucovorin (20 mg/m2) and irinotecan (125
mg/m2)] or in combination with bevacizumab containing chemotherapy.

Vectibix should not be administered in combination with
oxaliplatin-containing chemotherapy to mCRC patients with mutant KRAS
tumors or for whom KRAS tumor status is unknown.

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, bone disease
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.

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CONTACT: Amgen
Carrie Deverell: +41-41-3690-308 (E.U. media)
Christine Regan: +1-805-447-5476 (U.S. media)
Arvind Sood: +1-805-447-1060 (investors)

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(i) Peeters, M et al. Randomized Phase III Study of Panitumumab
With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With
FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic
Colorectal Cancer. J Clin Oncol 28, 2010.

(ii) Adverse event rates were comparable across arms with the
exception of known toxicities associated with EGFR therapy such as
rash, diarrhea and hypomagnesemia. Vectibix-related grade 3 infusion
reactions were reported for two patients (less than one percent).

(iii) In general, adverse events 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 3/4 infusion
reactions were reported in less than one percent of patients.

(iv) Malumbres, M. and Barbacid, M. RAS oncogenes: the first 30
years. Nature Reviews Cancer. 3:459-65, 2003.

(v) Karapentis C, S. Snell, L, E. The Laboratory Assessment of
KRAS Mutation Status in Colorectal Cancer. Asia, Pacific Journal of
Oncology and Hematology. 2010.

(vi) Friday BB and Adjei AA. K-ras as a target for cancer
therapy. Biochim. Biophys. Acta 1756: 127-144, 2005

(vii) Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin
DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC
CancerBase No. 10. Lyon, France: International Agency for Research on
Cancer; 2010

(viii) Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of
cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010
Mar; 46(4):765-81. Epub 2010 Jan 29.

(ix) Vectibix (panitumumab) [prescribing information]. Thousand
Oaks, Calif: Amgen; 2011.

(x) Vectibix (panitumumab) SPC. Thousand Oaks, Calif: Amgen; 2011

ots Originaltext: Amgen
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