Bayer Schering Pharma today announced that data presented from an analysis of the results from the Phase 3 Sorafenib HCC Assessment Randomized Protocol (SHARP) and Asia-Pacific trials demonstrated that Nexavar® (sorafenib) tablets provide a significant overall survival benefit for the treatment of advanced hepatocellular carcinoma (HCC), in both trials. Nexavar is the only oral, targeted therapy approved for the treatment of advanced HCC. Nexavar is the first approved systemic drug therapy in Singapore for liver cancer.

The etiology of liver cancer varies considerably by geographic region; therefore this analysis compared the results of the SHARP and Asia Pacific trials. The two studies enrolled patients from different geographic areas: SHARP enrolled patients from Europe, North/South America and Australia and the Asia Pacific trial enrolled patients from the Asia Pacific region (China, Taiwan and Korea). Overall, the patients in the Asia Pacific trial had poorer health status and more metastases.

Despite this, the efficacy results were comparable in both trials, showing that treatment with Nexavar increased overall survival (OS) and time to progression (TTP) in both studies. Specific results from the trials include:

"These two studies clearly demonstrate that treatment with Nexavar is effective in treating liver cancer in different patient populations with different stages of disease," said Dr. Jordi Bruix, lead study investigator and Director, BCLC Group, Liver Unit, Hospital Clínic, University of Barcelona, Spain. "While the patients in the Asia Pacific trial were sicker, the percent improvement in overall survival and time to progression, as well as the reduction in the risk of death and disease progression with Nexavar was comparable between the two studies."

Dr. Bruix added that because the patients in the Asia Pacific trial were sicker, the survival times in both the Nexavar and placebo-treated patients were not as long as those seen in SHARP trial. "However the comparative survival benefit mirrored the SHARP results with a significant improvement of overall survival in the patients treated with Nexavar," he said. Welcoming the results, Dr. Hsieh Wen Son, Consultant Oncologist, International Cancer Consultants, Singapore, said, "Treatment options for liver cancer patients are limited. Nexavar is the only systemic therapy that has been shown to improve overall survival in patients with liver cancer. These latest results further confirm the safety and efficacy of Nexavar in Asian patients, offering those in Singapore an option in the systemic treatment of advanced liver cancer."

The Study Design

The study designs for both trials were similar with patients who had received no prior systemic therapy being randomized to receive Nexavar 400 mg twice daily or placebo. Randomization differed between the two studies because the Chinese regulatory authority required that the randomization in the Asia Pacific trial be 2:1 to allow more patients to benefit from the active drug. Both studies were designed to compare overall survival, time to progression, time to symptomatic progression, response as defined by RECIST criteria and safety in patients receiving Nexavar versus placebo. The survival benefit was seen across multiple patient subsets analyzed, including age, extrahepatic spread and/or macroscopic vascular invasion. Drug-related adverse events (AEs) reported by patients receiving Nexavar were predominantly grade 1 or 2. The most frequently reported AEs for patients treated with Nexavar were hand-foot skin reaction and diarrhea.

About Liver Cancer

Liver cancer is the sixth most common cancer in the world and the third leading cause of cancerrelated deaths globally. Approximately 626,000 cases of liver cancer are diagnosed worldwide each year (more than 370,000 in China, South Korea, Hong Kong and Taiwan, 54,000 in the European Union, and 15,000 in the United States) and the incidence is increasing. In 2002, approximately 600,000 people died of liver cancer including more than 341,000 in China, South Korea, Hong Kong and Taiwan, 57,000 in the European Union, and 13,000 in the United States.1,2,3,4 In Singapore, liver cancer is the fourth most common cancer occurring in men. There were approximately 417 new cases of cancer each year from 2002 to 2006. Liver cancer often results from certain liver-related illnesses such as hepatitis B, hepatitis C, alcohol abuse, fatty liver disease, and exposure to chemicals.

Treatment options for liver cancer patients are limited and depend on the stage of the malignant disease, underlying liver function and the patient's overall condition.5 Standard treatments for liver cancer include: surgery (i.e. resection or liver transplant), logoregional treatment options such as percutaneous ethanol injection (PEI) or transarterial chemoembolization (TACE), and systemic therapy.6,7

Nexavar's Differentiated Mechanism

Nexavar, an oral anti-cancer therapy, is currently approved in more than 60 countries for liver cancer and in more than 70 countries for the treatment of patients with advanced kidney cancer. Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) ??" two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.

Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators as a single agent or combination treatment in a wide range of other cancers, including metastatic melanoma, breast cancer and as an adjuvant therapy for kidney cancer and liver cancer.

About Bayer Schering Pharma AG

Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, Hematology/Cardiology, Oncology, Primary Care, Specialized Therapeutics and Women's Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life. Find more information at http://www.bayerscheringpharma.de.

References

1 Ferlay J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5, Version 2.0. IARCPress, Lyon, 2004. Available at: http://www-dep.iarc.fr. Accessed May 2008.

2 2005 Cancer Register System (CRS) annual report, http://crs.cph.ntu.edu.tw/crs_c/annual.html. Accessed May 12, 2008.

3 The statistical survey datas are from the Korea National Cancer Information Center, research lab from the Korea National Center. http://www.cancer.go.kr/cms/statics/stat/1193967_1611.html

4 The data from Hong Kong Cancer Registry, Hospital Authority of Hong Kong 2006.

5 American Cancer Society. What is Liver Cancer? Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_2_1X_What_is_liver_cancer_25.asp. Accessed April 10, 2007.

6 Blum HE. Hepatocellular carcinoma: therapy and prevention. World J Gastroenterol. 2005;11:7391-400.

7 Thuluvath PJ,Choti M, Geschwind JF, Norwitz L and Kalloo AN. About Liver Cancer. Johns Hopkins Liver Cancer Center. http://gastro.nts.jhu.edu/about.cfm.

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