For the third year in a row, the American Society of Clinical Oncology (ASCO) has included Erbitux (cetuximab) research in its annual report, Clinical Cancer Advances, which features the most significant studies of 2010. The report cites as a notable advance this year the finding that BRAF mutation status is a prognostic, not predictive, marker for Erbitux efficacy in metastatic Colorectal Cancer (mCRC). This finding is from the pooled analysis of the large, randomized CRYSTALa and OPUSb clinical studies, which were supported by Merck Serono, a division of Merck KGaA, Darmstadt, Germany.

“This is the result of our focused work on biomarker-guided research to improve cancer care,” said Dr. Oliver Kisker, senior vice-president, Global Clinical Development Unit for Oncology, Merck Serono. “We are honoured to have our Erbitux clinical development program recognized in three different cancers in three successive years by the oncology community” he added.

In 2009, Erbitux was included in the report as a major advance for the year that had the potential to lead to a reduction in mortality from cancer. It was recognized as an advance in personalized medicine and targeted therapies in head and neck cancer. The results from the randomized Extremec trial presented during the ASCO 2009 meeting showed that Erbitux is the first treatment in more than 30 years to demonstrate an improvement in overall survival for advanced head and neck cancer patients.

In 2008, Erbitux was twice highlighted as a major advance in the treatment of both mCRC and non-small cell lung cancer (NSCLC). Erbitux was listed as the only significant advance in personalized medicine for 2008. The results of the Crystal study validated KRAS mutation status as predictive of Erbitux efficacy in mCRC patients. In hard-to-treat cancers, it was listed as the only treatment to advance lung cancer care. Results from the randomized FLEXd study showed that adding Erbitux to chemotherapy increased overall survival in patients with NSCLC that expressed the epidermal growth factor receptor (EGFR).

“We continue to believe that using biomarkers to convert therapies targeted at specific pathways into personalized medicines will lead to greater progress in improving cancer care for patients,” said Dr. Kisker. “We look forward to yet another year of advances in oncology.”

aCRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metastatic colorectal cancer. bOPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC. cEXTREME: ErbituX in 1st-line Treatment of REcurrent or MEtastatic head and neck cancer. dFLEX: First-Line ErbituX in lung cancer

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 tumour cells and the spread of tumours to new sites. It is also believed to inhibit the ability of tumour cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumours, which appears to lead to an overall suppression of tumour 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 82 countries. It has been approved for the treatment of colorectal cancer in 82 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 79 countries: December 2003 (Switzerland), February 2004 (USA), June 2004 (EU) and followed by other countries: for use in combination with irinotecan in patients with EGFR-expressing mCRC (metastatic colorectal cancer) who have failed prior irinotecan therapy.

In addition, Erbitux is also approved for single-agent use in further countries. April 2006 (EU) and followed by other countries: for use in combination with radiotherapy for the treatment of locally advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN). In further countries, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.

July 2008 (EU): license was updated for the treatment of patients with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type mCRC in combination with chemotherapy and as a single agent in patients who have failed oxaliplatin-and irinotecan-based therapy and who are intolerant to irinotecan. July 2008 (Japan): for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. In November 2008 (EU): license was updated for the use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN. March 2010 (Japan): label extended to use in combination with chemotherapy in the 1st-line treatment for patients with epidermal growth factor receptor (EGFR)-expressing, curatively unresectable (inoperable), advanced or recurrent colorectal cancer (mCRC) is carrying the KRAS wild-type gene.

Merck licensed the right to market Erbitux outside the US 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, 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 (tegafur-uracil) – an oral chemotherapy administered with Folinic Acid (FA) for the first-line treatment of metastatic colorectal cancer.

Merck is also investigating among other potential cancer treatments the use of Stimuvax (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 Oncothyreon Inc., Seattle, Washington, USA.

In addition, Merck is developing cilengitide, which is the first in a new class of investigational anti-cancer therapies called integrin inhibitors to reach Phase III development; it is currently being investigated for the treatment of glioblastoma, SCCHN and NSCLC. Integrin inhibitors are thought to work by targeting the tumor and its vasculature.

Merck Serono is the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. In the United States and Canada, EMD Serono operates through separately incorporated affiliates.

Merck Serono has leading brands serving patients with cancer (Erbitux, cetuximab), multiple sclerosis (Rebif, interferon beta-1a), infertility (Gonal-f, follitropin alfa), endocrine and metabolic disorders (Saizen and Serostim, somatropin), (Kuvan, sapropterin dihydrochloride) as well as cardiometabolic diseases (Glucophage, metformin), (Concor, bisoprolol), (Euthyrox, levothyroxine). Not all products are available in all markets.

With an annual R&D expenditure of over € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in rheumatology.

Merck is a global pharmaceutical and chemical company with total revenues of € 7.7 billion in 2009, a history that began in 1668, and a future shaped by approximately 40,000 (including Merck Millipore) employees in 64 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.