Bayer and Onyx submit supplemental NDA for Nexavar

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals have announced that a Supplemental New Drug Application (sNDA) for Nexavar (sorafenib) tablets has been submitted to the U.S. Food and Drug Administration (FDA) for the treatment of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer. Nexavar is currently approved in more than 50 countries for the treatment of advanced kidney cancer.

The companies also confirmed that they are planning a company- sponsored Phase 3 study of Nexavar in the adjuvant treatment of HCC following the complete removal of early stage liver cancer.

The sNDA submission is based on positive data from the international, Phase 3, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial which demonstrated that Nexavar extended overall survival by 44 percent in patients with HCC (HR=0.69; p=0.0006) versus placebo. There were no significant differences in serious adverse event rates between the Nexavar and placebo-treated groups with the most commonly observed adverse events in patients receiving Nexavar being diarrhea and hand-foot skin reaction. Currently, there are no FDA-approved drug therapies that significantly extend survival of patients with liver cancer.

"These results are particularly meaningful considering that death rates from liver cancer continue to increase," said Susan Kelley, M.D., vice president, Therapeutic Area Oncology, Bayer HealthCare Pharmaceuticals. "After more than 100 clinical studies of many agents over three decades, Nexavar is the first drug therapy to demonstrate a significant survival benefit for patients with HCC, and, if approved, may fulfill a serious unmet need with a manageable toxicity profile."

HCC, the most common form of liver cancer, is responsible for about 90 percent of the primary liver cancers 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 cases of HCC are diagnosed globally each year(4) (about 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)

"This filing exemplifies our commitment to providing valuable therapeutic options for significant unmet needs in cancer treatment," said Hank Fuchs, M.D., executive vice president and chief medical officer of Onyx. "We believe that Nexavar will become the reference standard of care in HCC, and will help advance our development program, which includes clinical trials studying Nexavar alone and in combination with other therapies across many different cancer types, including melanoma, non-small cell lung and breast 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. Preclinical models have also demonstrated that Raf/MEK/ERK has a role in HCC; therefore blocking signaling through Raf-1 may offer therapeutic benefits in HCC.

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).