Erbitux

Treatment for Colorectal Cancer, Head and Neck Cancer

Merck Applies to Extend Use of Erbitux for 1st-Line Colorectal Cancer

DARMSTADT, Germany, September 3, 2007 - Merck KGaA announced today that it has submitted an application to the European Medicines Agency (EMEA) to broaden the use of the targeted cancer therapy, Erbitux® (cetuximab), to include first-line therapy for the treatment of metastatic colorectal cancer (mCRC).

The submission is supported in part by data from the CRYSTAL study that demonstrates the efficacy of Erbitux as a first-line treatment in mCRC patients (CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer). The study showed that, when added to current standard irinotecan based chemotherapy in first-line, Erbitux significantly increased progression-free survival, response and resection rates. This means that as well as improving efficacy of first-line chemotherapy, Erbitux is the only targeted therapy to increase the chance of cure through resection.

“The positive results we have seen for Erbitux as a first-line therapy are really important,” said Dr Wolfgang Wein, Senior Executive Vice President, Oncology, Merck Serono. “If approved, using Erbitux as a first-line therapy will provide a much greater hope for cure for these patients.”

The CRYSTAL trial, a phase III study of Erbitux plus FOLFIRI (irinotecan-based therapy) compared with FOLFIRI alone, met the primary endpoint of significantly increasing median duration of progression-free survival in patients with previously untreated mCRC. Findings from this randomized, controlled trial of almost 1,200 patients were presented at the ASCO congress in June 2007.

The side effects of Erbitux in combination with chemotherapy were manageable and consistent with the current safety information.

The application for first-line indication will be reviewed by the Committee for Medicinal Products for Human Use (CHMP). If approved by the European Commission, patients within Europe may start benefiting from Erbitux as a first-line therapy from the second half of next year.

The submission also includes the broadened use of Erbitux in pre-treated mCRC patients based on two further Phase III studies. These studies demonstrated the efficacy of Erbitux in patients previously treated with oxaliplatin1 or oxaliplatin and irinotecan2.

Erbitux was first approved for treatment of mCRC after irinotecan failure in Switzerland in December 2003. It was also approved for treatment of mCRC after irinotecan failure in the United States by the Food and Drug Administration (FDA) in February 2004 and was followed by EMEA approval in June 2004.

Colorectal Cancer Every year in Europe, more than 370,000 people develop colorectal cancer, accounting for 13% of the total cancer burden and around 200,000 deaths.3 Approximately 25% of patients present with metastatic disease.4 Five-year survival rates for patients with mCRC are as low as 5%.5

References: 1) Sobrero AF et al. Data presented at AACR 2007 Abstract LB-2 2) Jonker DJ et al. Data presented at AACR 2007, Abstract LB-1 3) Parkin DM et al. CA Cancer J Clin 2005; 55: 72-108 4) GLOBOCAN. http://www-dep.iarc.fr/ 5) Argiris A et al. Cancer 2004; 101: 2222-2229

Notes for editors 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 68 countries. It has been approved for the treatment of colorectal cancer in 67 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, the European Union, Guatemala, Honduras, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Lebanon, Malaysia, Mexico, Montenegro, New Zealand, Nicaragua, Norway, Panama, Peru, the Philippines, Russia, Serbia, Singapore, South Korea, Switzerland, Taiwan, Thailand, Ukraine, the US, and Venezuela for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. Erbitux is also approved for single-agent use in: Argentina, Australia, Canada, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Lebanon, Mexico, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela.

In addition, Erbitux in combination with radiotherapy has been approved for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in 58 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Malaysia, Mexico, Montenegro, Nicaragua, Norway, Panama, the Philippines, Russia, Serbia, Singapore, Switzerland, Taiwan, Ukraine, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Mexico, Nicaragua, the Philippines, Russia, and the US, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, Merck has co-exclusive marketing rights with ImClone Systems. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT® (tegafururacil) – an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.

Merck is also investigating among other cancer treatments the use of Stimuvax® (formerly referred to as BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Biomira Inc. of Edmonton, Alberta, Canada.

Merck is a global pharmaceutical and chemical company with sales of EUR 6.3 billion in 2006, a history that began in 1668, and a future shaped by 35,214 employees in 63 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.

Posted: September 2007

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