Amgen to Appeal CHMP Opinion on Vectibix(R) (Panitumumab) Use With Chemotherapy in Metastatic Colorectal Cancer in Europe

THOUSAND OAKS, California, March 30, 2011 /PRNewswire/ --

Amgen (Nasdaq: AMGN) announced today that it has submitted a request to the European Medicines Agency (EMA) for a re-examination of the negative opinion issued in March by the Committee For Medicinal Products for Human Use (CHMP) for the use of Vectibix in combination with chemotherapy for patients with wild-type KRAS metastatic colorectal cancer (mCRC).

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.

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. Though quantitatively greater, the improvement in median overall survival did not achieve statistical significance in the Vectibix arm of either trial.(i)(ii)

In general, adverse event 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 mutant KRAS tumors, outcomes were inferior for those receiving Vectibix plus FOLFOX versus FOLFOX alone.(iii)(iv)

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 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.(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)

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 progression-free survival (PFS). 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 pending.

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, 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.

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 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 vital medicines, visit http://www.amgen.com.

Forward-Looking Statements

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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 percent).
    (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. (http://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. 
           (http://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.

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