Nexavar Significantly Extends Overall Survival By 44% In liver Cancer Patients

Bayer HealthCare Pharmaceuticals Inc. (NYSE: BAY) and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today 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 world(3) and the third leading cause of cancer-related deaths globally.(4) Over 600,000 new cases of HCC are diagnosed globally each year(4) (19,000 in the United States(5) and 32,000 in the European Union(6)), 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.”

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 www.nexavar.com or call 1.866.NEXAVAR (1.866.639.2827).