Nexavar Significantly Extends Overall Survival By 44 Percent In Liver Cancer Patients

Main Category: Liver Disease / Hepatitis
Also Included In: Clinical Trials / Drug Trials
Article Date: 05 Jun 2007 - 19:00 PDT

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Bayer HealthCare Pharmaceuticals Inc. (NYSE: BAY) and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) has announced that Nexavar® (sorafenib) tablets significantly extended overall survival in patients with hepatocellular carcinoma (HCC), or primary liver cancer versus those taking placebo by 44% (HR=0.69; p-value=0.0006). Results were presented at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO).

The international, Phase 3, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) Trial randomized and evaluated 602 liver cancer patients who had no prior systemic therapy at sites in the Americas, Europe, and Australia/New Zealand. The primary objective of the study was to compare overall survival in patients administered Nexavar versus those administered placebo. Median overall survival was 10.7 months in Nexavar-treated patients compared to 7.9 months in those taking placebo.

"Because there are no therapies that significantly improve survival for the thousands of patients with liver cancer, these findings demonstrate the compelling study results of Nexavar as the new reference standard of care for the first-line treatment of HCC," said Dr. Josep M. Llovet, co-principal investigator and Professor of Research, Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, Liver Unit, Hospital Clinic Barcelona; Director of Research, HCC Program, Associate Professor of Medicine, Mount Sinai School of Medicine, New York.

Bayer and Onyx halted the SHARP trial in February 2007 when an independent data monitoring committee determined in a pre-scheduled analysis that the overall survival endpoint had been met. There were no significant differences in serious adverse event rates between the Nexavar and placebo-treated groups, with the most commonly observed serious adverse events in patients receiving Nexavar being diarrhea and hand-foot-skin reaction. Based on the strength of the data, the companies are now in the process of preparing applications to the U.S. Food and Drug Administration (FDA) and European health authorities for a supplemental indication for Nexavar in treatment of patients with liver cancer.

"Although much progress has been made in cancer research, the number of lives lost to liver cancer is increasing," said Dr. Jordi Bruix, co-principal investigator and Director of the Barcelona Clinic Liver Cancer (BCLC) Group; Senior Consultant, Liver Unit, Hospital Clinic of Barcelona. "For that reason, these results represent an unprecedented achievement and Nexavar could become the first widely-approved new therapy for this difficult to treat cancer."

Hepatocellular carcinoma is the most common form of liver cancer and is responsible for about 90 percent of the primary malignant liver tumors in adults.1, 2 It is the fifth most common cancer in the world3 and the third leading cause of cancer-related deaths globally.4 Over 600,000 new cases of HCC are diagnosed globally each year4 (19,000 in the United States5 and 32,000 in the European Union6), and in 2002 approximately 600,000 people (about 13,000 Americans and 57,000 Europeans) died of HCC.7 Although overall cancer incidence and mortality are decreasing in the United States, both the incidence and mortality of liver cancer are increasing.8

Nexavar's Differentiated Mechanism

Nexavar targets both the tumor cell and tumor vasculature and is the only oral multi-kinase inhibitor that does not require patients to interrupt their treatment schedule.

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. Preclinical models have also demonstrated that the Raf/MEK/ERK pathway has a role in HCC; therefore blocking signaling through Raf-1 may offer therapeutic benefits in HCC.

Nexavar is currently approved in more than 50 countries, including the United States and those in the European Union, for the treatment of patients with advanced kidney cancer. In Europe, Nexavar is approved for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy.

Nexavar is also being evaluated by the companies, international study groups, government agencies and/or individual investigators as a single agent or combination treatment in a wide range of other cancers, including adjuvant therapy for kidney cancer, metastatic melanoma, breast cancer and non-small cell lung cancer (NSCLC). The Phase 3 ESCAPE (Evaluation of sorafenib, carboplatin, and paclitaxel efficacy in NSCLC) trial recently completed enrollment of more than 900 previously untreated patients with NSCLC of all histologies.

"HCC is the second tumor type in which Nexavar has demonstrated a clinical benefit. We intend to move swiftly with our partner Onyx to file these data for health authority review," said Susan Kelley, MD, Vice President, Therapeutic Area Oncology, Bayer HealthCare Pharmaceuticals. "Our strategy of leveraging the unique attributes of Nexavar, the only approved orally administered anti-angiogenic that targets the Raf pathway, has led to a robust ongoing clinical program that could bring the potent cancer fighting properties of this oral multi-kinase inhibitor to an even broader number of patients in the coming years."

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Important Safety Considerations for U.S. Patients Taking Nexavar

Based on the currently approved package insert for the treatment of patients with advanced kidney cancer, hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed. Incidence of bleeding regardless of causality was 15% for Nexavar vs. 8% for placebo and the incidence of treatment-emergent cardiac ischemia/infarction was 2.9% for Nexavar vs. 0.4% for placebo. Most common treatment-emergent adverse events with Nexavar were diarrhea, rash/desquamation, fatigue, hand-foot skin reaction, alopecia, and nausea. Grade 3/4 adverse events were 38% for Nexavar vs. 28% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding. In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.

For U.S. Nexavar prescribing information, visit http://www.nexavar.com/.

About Onyx Pharmaceuticals, Inc.

Onyx Pharmaceuticals, Inc. is a biopharmaceutical company developing innovative therapies that target the molecular mechanisms that cause cancer. The company is developing Nexavar®, a small molecule drug, with Bayer Pharmaceuticals Corporation. Nexavar has been approved for the treatment of advanced kidney cancer. For more information about Onyx's pipeline and activities, visit the company's web site at: http://www.onyx-pharm.com/.

About Bayer HealthCare

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals unit of Bayer HealthCare LLC, a division of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the United States, Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

About Bayer Schering Pharma AG, Germany

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 quality of life.

Forward Looking Statements

This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including its Form 20-F). Bayer assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

This news release also contains "forward-looking statements" of Onyx within the meaning of the federal securities laws. These forward-looking statements include without limitation, statements regarding the timing, progress and results of the clinical development, regulatory processes, and commercialization efforts of Nexavar. These statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated. Reference should be made to Onyx's Annual Report on Form 10-K for the year ended December 31, 2005, filed with the Securities and Exchange Commission under the heading "Risk Factors" and Onyx's Quarterly Reports on Form 10-Q for a more detailed description of such factors. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date of this release. Onyx undertakes no obligation to update publicly any forward-looking statements to reflect new information, events, or circumstances after the date of this release except as required by law. Nexavar® (sorafenib) tablets is a registered trademark of Bayer Pharmaceuticals Corporation.

Contacts:

Mark Bennett
Bayer HealthCare Pharmaceuticals

Julie Wood
Onyx Pharmaceuticals, Inc.

Jost Reinhard
Bayer Schering Pharma

References

1. World Health Organization. Hepatitis B. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/. Accessed April 10, 2007

2. Penn State Milton S. Hershey Medical Center College of Medicine. Malignant Hepatoma. Available at: http://www.hmc.psu.edu/healthinfo/m/malignanthepatoma.htm. Accessed April 10, 2007.

3. World Health Organization. Estimates by WHO Region: Incidence. Available at: http://www.who.int/healthinfo/statistics/gbdwhoregionincidence2002.xls. Accessed April 10, 2007.

4. International Agency for Cancer Research. GLOBOCAN 2002. Available at: http://www.who.int/healthinfo/statistics/gbdwhoregionincidence2002.xls. Accessed April 23, 2007.

5. Jemal A et al. CA Cancer J Clin. 2007;57:43-66.

6. International Agency for Cancer Research. EUCAN 1998. Available at: http://www-dep.iarc.fr/eucan/eucan.htm. Accessed April 26, 2007.

7. 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 April 10, 2007.

8. Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER web site, 2007.

Contact: Charlotte Rocker
GCI Group

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