Amgen Statement on CHMP Opinion on Vectibix(R) (Panitumumab) Use With Chemotherapy in Metastatic Colorectal CancerBy Amgen, PRNE
Thursday, March 17, 2011
THOUSAND OAKS, California, March 18, 2011 - Amgen (Nasdaq: AMGN) today issued the following statement:
Amgen has received notice that the Committee for Medicinal Products for
Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a
negative opinion for Amgen's application to extend the marketing
authorization in Europe for Vectibix(R) (panitumumab) to include combination
with chemotherapy for the treatment of patients with wild-type KRAS
metastatic colorectal cancer (mCRC).
Amgen will review the CHMP opinion and consider appropriate next steps,
as Amgen believes that Vectibix in combination with chemotherapy provides an
important treatment option for patients with wild-type KRAS mCRC. Amgen
remains committed to patients with this aggressive disease, for whom there
are limited treatment options.
Vectibix is already approved and established in more than 30 countries
outside of the United States (U.S.) as a monotherapy treatment for patients
with wild-type KRAS mCRC, when standard chemotherapy is no longer effective.
In the 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. Furthermore, use of Vectibix is
not recommended in patients whose tumors have KRAS mutations in codon 12 or
13. In Japan and Israel, Vectibix is approved for use in combination with
chemotherapy for patients with wild-type KRAS mCRC.
Data from studies 20050203 (PRIME) and 20050181 ('181') showed that
adding Vectibix to FOLFOX and FOLFIRI chemotherapy, respectively, improved
progression-free survival (PFS) versus chemotherapy alone in patients with
wild-type KRAS mCRC. Patients taking this combination have a greater chance
of living longer without their disease getting worse. Additionally, the
response rate 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
In general, adverse events rates were comparable across arms in both
studies, with the exception of known toxicities associated with anti-EGFR
therapy, such as rash, diarrhea, and hypomagnesemia. Vectibix-related grade
3/4 infusion reactions were reported in less than one percent of patients. In
patients with mutated KRAS tumors, outcomes were inferior for those receiving
Vectibix plus FOLFOX versus FOLFOX alone. (iii)(iv)
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.(v) 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 40-50 percent of mCRC patients.(vi)(vii)
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.(viii) In 2008, there were an
estimated 333,330 new cases of colorectal cancer in the EU.(ix)
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
The effectiveness of Vectibix as a single agent for the treatment of
EGFR-expressing mCRC is based on progression-free survival. 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 colorectal
cancer with these mutations.(x)
In December 2007, the European Medicine Agency (EMA) 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.(xi) Vectibix has been launched
in more than 30 European Union countries, Russia, Israel, Switzerland,
Australia, Canada and Japan. Applications in the rest of the world are
Important European Product Safety Information
For full prescribing information please see the Summary of Product
Vectibix is indicated as monotherapy for the treatment of patients with
EGFR-expressing, metastatic colorectal carcinoma (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 tumours
or for whom KRAS tumour status is unknown.
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This statement contains forward-looking statements that are based on
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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)
(i) Douillard, JE et al. Randomized, Phase 3 Study (PRIME) of Panitumumab
with FOLFOX4 versus FOLFOX4 Alone as First-Line Treatment in Patients With
Previously Untreated Metastatic Colorectal Cancer. J Clin Oncol 28. 2010.
(ii) 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.
(iii) 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
(iv) 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.
(v) Malumbres, M. and Barbacid, M. RAS oncogenes: the first 30 years.
Nature Reviews Cancer. 3:459-65, 2003.
(vi) Karapentis C, S. Snell, L, E. The Laboratory Assessment of KRAS
Mutation Status in Colorectal Cancer.
Asia, Pacific Journal of Oncology and Hematology. 2010.
(vii) Friday BB and Adjei AA. K-ras as a target for cancer therapy.
Biochim. Biophys. Acta 1756: 127-144, 2005.
(viii) Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM.
GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No.
10. (globocan.iarc.fr) Lyon, France: International Agency for Research
on Cancer; 2010.
(ix) Ferlay J, Parkin DM, Steliarova-Foucher E Estimates of cancer
incidence and mortality in Europe in 2008.
(www.ncbi.nlm.nih.gov/pubmed/20116997) Eur J Cancer. 2010 Mar;
46(4):765-81. Epub 2010 Jan 29.
(x) Vectibix (panitumumab) [prescribing information]. Thousand Oaks,
Calif: Amgen; 2011.
(xi) Vectibix (panitumumab) SPC. Thousand Oaks, Calif: Amgen; 2011.
E.U. media, Carrie Deverell, +41-41-3690-308, or U.S. media, Christine Regan, +1-805-447-5476, or investors, Arvind Sood, +1-805-447-1060, all of Amgen
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