European Commission Approves Update of Erbitux Metastatic Colorectal Cancer Labeling to Patients With RAS Wild-Type Tumors

DARMSTADT, Germany, December 23, 2013 /PRNewswire/ --

• The European Commission's approval is based on the CHMP positive opinion
• Label update comes in response to new biomarker data obtained from the OPUS study

Merck Serono, the biopharmaceutical division of Merck, today announced that the European Commission has approved the Type II variation to amend the Erbitux^® (cetuximab) product information, updating the indication for Erbitux to the treatment of patients with RAS wild-type metastatic colorectal cancer (mCRC). The approval of the European Commission follows the positive opinion from the Committee for Medicinal Products for Human Use (CHMP) (issued in November 2013) and is based on the totality of data emerging on the role of mCRC RAS tumor status in the benefit-risk profile of the drug. The approval primarily refers to new biomarker data from the OPUS (OxaliPlatin and cetUximab in firSt-line treatment of mCRC) study.^[1]

In recent analyses of studies evaluating monoclonal anti-epidermal growth factor receptor (EGFR) antibodies, such as Erbitux, tumor samples of patients with KRAS wild-type tumor status (exon 2) were assessed for additional RAS mutations (defined as mutations in exons 3 or 4 of KRAS and/or exons 2, 3 or 4 of NRAS). The results from these studies suggest that patients with RAS wild-type tumors may benefit from treatment with Erbitux, while patients with RAS mutant tumors may not.

"We fully endorse the update to the indication of Erbitux in metastatic colorectal cancer, as it will provide further guidance to physicians who manage patients with colorectal cancer," said Belén Garijo, President and CEO of Merck Serono. "We will now be working with the regulatory agencies to effectively communicate the implications of this label change to healthcare professionals and patients."

In the updated product information, Erbitux will now be indicated for the treatment of patients with EGFR-expressing, RAS wild-type mCRC in combination with irinotecan-based chemotherapy, in 1st line in combination with FOLFOX, or as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan. In this label change, the existing contraindication for the combination of Erbitux with oxaliplatin-containing chemotherapy is now extended to include patients with mutant RAS mCRC or for whom RAS mCRC status is unknown.

The full Erbitux patient information will be publicly available in the revised SmPC. Once updated, this will be available online at http://www.ema.europa.eu/ema

About the OPUS Study

OPUS is a randomized, controlled, Phase II trial, involving 337 mCRC patients, 179 with KRAS wild-type (exon 2) tumors, demonstrating the efficacy of Erbitux plus FOLFOX-4 (oxaliplatin-based therapy) versus FOLFOX-4 alone.^[2] Results of a RAS tumor status analysis will be presented at Gastrointestinal Cancers Symposium (ASCO GI) in January 2014, in San Francisco, California, U.S..

About Colorectal Cancer

Colorectal cancer (CRC) is the fourth most common cancer worldwide, with an estimated incidence of more than 1.2 million cases globally.^[3] An estimated 608,000 deaths from CRC occur worldwide each year, accounting for 8% of all cancer deaths and making it the fourth most common cause of death from cancer.^[3] Almost 60% of the cases occur in developed regions, and incidence and mortality rates are substantially higher in men than in women.^[3] In Europe alone, an estimated 436,000 people develop CRC every year, with approximately 212,000 people dying from the disease annually.^[4]

References

1. Tejpar S, et al. Accepted at 2014 Gastrointestinal Cancers Symposium, January 16-18, 2014.

2. Bokemeyer C, et al. Ann Oncol 2011;22(7):1535-46.

3. Ferlay J, et al. Int J Cancer 2010;127(12):2893-917.

4. Ferlay J, et al. Eu J Cancer 2010;46(4):765-81.

For more information on Erbitux in colorectal and head & neck cancer, please visit http://www.globalcancernews.com.

About Erbitux

Erbitux^® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.

The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in over 90 countries for the treatment of colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck (SCCHN).

Merck licensed the right to market Erbitux outside the U.S. and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas.

About Merck Serono

Merck Serono is the biopharmaceutical division of Merck. With headquarters in Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help patients with cancer, multiple sclerosis, infertility, endocrine and metabolic disorders as well as cardiovascular diseases. In the United States and Canada, EMD Serono operates as a separately incorporated subsidiary of Merck Serono.

Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. We have an enduring commitment to deliver novel therapies in our core focus areas of neurology, oncology, immuno-oncology and immunology.

For more information, please visit http://www.merckserono.com.

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Merck is a leading pharmaceutical, chemical and life science company with total revenues of € 11.2 billion in 2012, a history that began in 1668, and a future shaped by approx. 38,000 employees in 66 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

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