• 5/18/2005
  • Orlando, FL & Darmstadt, Germany
  • PharmaLive (www.medadnews.com)

Merck KGaA of Darmstadt, Germany, today announced its continued investment in innovative therapies in oncology, supported by data presented at the 41st annual meeting of the American Society of Clinical Oncology (ASCO). Merck KGaA, known for the first-in-class EGFR-targeted monoclonal antibody, Erbitux® (cetuximab) that works by blocking the epidermal growth factor receptor (EGFR) to inhibit tumor growth and spread, has ongoing active development programs with additional novel therapies that may offer new hope to people with cancer.

“These are exciting times in oncology,” said Dr. Bernhard Ehmer, Vice President, Business Area Oncology, Merck KGaA. “With a better understanding of the growth and spread of tumors, we are able to develop treatments that target the cancer cells and give physicians and their patients additional options with which to fight cancer. We are particularly excited by Erbitux not only in the treatment of colorectal cancer but also in its potential in head and neck cancer and by BLP25 Liposome Vaccine (L-BLP25), which is showing impressive results in the treatment of non-small cell lung cancer. Furthermore, our humanized EGFR-targeting monoclonal antibody matuzumab is showing potential in several types of cancer.”

Erbitux
Consistent findings in clinical trials supports the use of Erbitux in different treatment settings, and several presentations at ASCO focused on the results of studies of Erbitux in the treatment of various stages of colorectal cancer, squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC).

Study results presented at ASCO 2005 showed that Erbitux and a platinum compound (cisplatin or carboplatin) or Erbitux monotherapy in patients with recurrent and/or metastatic SCCHN may prolong survival by 2.5 months compared to platinum-refractory historical controls.1 This supports Phase III data in locally advanced SCCHN presented at ASCO 2004 where the median overall survival for patients treated with Erbitux and radiotherapy was 54 months compared to 28 months for patients treated with radiotherapy alone 2.

L-BLP25
An update on the Phase IIB trial showed that median survival had not been reached at 23 months, meaning that more than 50 percent of patients with Stage IIIB locoregional NSCLC who were given the vaccine were still alive at 24 months. For the non-vaccine arm, the median survival time was 13.3 months.

The difference in survival between the two groups remains non-significant (p=0.0924). However, the median survival of the vaccine arm will be no less than 23 months and the hazard ratio remains 0.5652 (A hazard ratio of less than one indicates a decrease in the risk of death). The one-year, two-year, and three-year survival differences continue to suggest a positive survival impact for those who received vaccine. 3

Matuzumab
Data from clinical trials involving matuzumab presented at ASCO includes:
– Advanced non-small cell lung cancer (NSCLC). Response to treatment with matuzumab and paclitaxel was not reliant on mutations in the kinase domain of the EGFR.4 These mutations are found in about 2 percent to 25 percent of NSCLC patients and some research has shown that the efficacy of EGFR tyrosine kinase inhibitors is correlated with the presence of mutations, whereas matuzumab appears not to rely on this mutation, based on the data presented.

– Advanced esophago-gastric adenocarcinoma. Preliminary results from two studies indicate that the combination of matuzumab and two commonly used chemotherapy regimens – cisplatin, 5-fluorouracil and leucovorin (PFL), and epirubicin, cisplatin and capecitabine (ECX) – appear to be well tolerated in the first-line setting.5,6

– Recurrent cervical cancer. Preliminary observations from a Phase II trial of matuzumab monotherapy in platinum-resistant cervical cancer demonstrated a 22 percent disease control rate (5 percent partial response and 17 percent stable disease). Matuzumab was generally well tolerated and warrants further investigation.7

“All these study results reinforce how essential it is for Merck to continue exploring alternative and more intelligent ways to attack cancers and prevent tumors from growing and spreading,” Ehmer said. “And we’re committed to do just that.”

Merck KGaA currently focuses on four therapeutic technology platforms in oncology:
– EGFR-targeting monoclonal antibodies that may block tumor growth;
– Immunocytokines that may provide local stimulation of the immune system;
– Angiogenesis inhibitors that may starve tumors of the blood supply they need to grow and spread; and
– Cancer vaccines that may stimulate a specific immune response against tumors.

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.

Erbitux has already obtained market authorization in Switzerland, the US, Mexico, Argentina, Chile, Iceland, Norway, the European Union, Peru, Australia, Croatia and Singapore for the use in combination with irinotecan in patients with EGFR-expressing metastatic colorectal cancer who have failed prior irinotecan therapy. In the US, Argentina, Chile, Mexico, Peru, Singapore and Australia, Erbitux is also approved for single agent usage.

Merck KGaA, Darmstadt, Germany, licensed the right to market Erbitux outside the US and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, Merck KGaA has co-exclusive marketing rights with ImClone Systems.

About L-BLP25
L-BLP25 is a synthetic MUC1 peptide vaccine, designed to induce an immune response to cancer cells. L-BLP25 incorporates a 25-amino acid sequence of the MUC1 cancer mucin, encapsulated in a liposomal delivery systerm. The liposome enhances recognition of the cancer antigen by the immune system and facilitates better delivery.

Merck is collaborating with Biomira Inc. of Edmonton, Alberta, Canada, in the development of L-BLP25, which was granted fast-track status by the US FDA in September 2004.

About Matuzumab
Matuzumab is a humanized EGFR monoclonal antibody currently in Phase II development for various solid tumors expressing the EGF receptor. Matuzumab enhances Merck’s position as a leader in the development of EGFR targeted therapies.

References
1. Vermorken J et al. Proc Am Soc Clin Oncol, Orlando, Florida, 2005: abstr 5505.
2. Bonner J et al. Proc Am Soc Clin Oncol 2004.
3. Murray N et al. Presented at ASCO, Orlando, Florida, 2005: abstr 7037.
4. Oechsle K et al. Proc Am Soc Clin Oncol, Orlando, Florida, 2005: abstr 8166.
5. Trarbach T et al. Proc Am Soc Clin Oncol, Orlando, Florida, 2005: abstr 3156.
6. Cunningham D et al. Presented at ASCO, Orlando, Florida, 2005: abstr 4001.
7. Blohmer J et al. Presented at ASCO, Orlando, Florida, 2005: abstr 2534.