Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) announced that the Ministry of Health, Labour and Welfare (MHLW) in Japan has approved Nexavar(R) (sorafenib) tablets for the treatment of patients with unresectable hepatocellular carcinoma (HCC), a type of liver cancer that accounts for 95 percent of all liver cancer cases in Japan(1). Nexavar is also currently available in Japan as an approved treatment for unresectable or metastatic renal cell carcinoma (RCC).

The approval in Japan was based on the international, Phase 3 double-blind, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) study that evaluated more than 800 patients who received no prior systemic therapy. The study found that Nexavar improved overall survival in patients with HCC by 44 percent (HR=0.69; p=0.0006) versus placebo. Based on SHARP results, Nexavar is currently approved in more than 70 countries for liver cancer, including the U.S. and countries in Europe.

“Liver cancer is one of the leading causes of cancer-related deaths in Japan, and the incidence is continuing to rise,” said Gunnar Riemann, member of the Executive Committee of Bayer HealthCare. “We are pleased with today’s approval and what it may mean for liver cancer patients in Japan and their families who now have a therapy like Nexavar that has the potential to extend their lives.”

In Japan, approximately 40,000 people are diagnosed with liver cancer each year and approximately 36,000 die from the disease, making primary liver cancer the third leading cause of cancer-related death in Japan.(2)

Hepatitis B viral infection (HBV) and hepatitis C viral infection (HCV) are leading risk factors for developing primary liver cancer worldwide, with HCV being the primary risk factor in Japan. An estimated 80 to 90 percent of Japanese patients diagnosed with liver cancer have HCV.(3)

“This is a significant milestone in the Japanese region where patients, who have high rates of liver cancer, are truly in need of a treatment option that improves survival,” said Laura Brege, executive vice president and chief operating officer at Onyx Pharmaceuticals, Inc. “This latest approval provides further evidence that Nexavar is an important therapy for patients with liver cancer as well as kidney cancer, an indication for which Nexavar was first approved in Japan.”

Hepatocellular carcinoma is the most common form of liver cancer(4) and is responsible for about 90 percent of the primary malignant liver tumors in adults(5). Liver cancer is the sixth most common cancer in the world(6) and the third leading cause of cancer-related deaths globally(7). More than 600,000 cases of liver cancer are diagnosed worldwide each year (more than 400,000 in China, South Korea, Japan and Taiwan, 54,000 in the European Union, and 15,000 in the United States) and the incidence is increasing(4). In 2002, approximately 600,000 people died of liver cancer including approximately 370,000 in China, South Korea and Japan, 57,000 in the European Union, and 13,000 in the United States(4).

Nexavar’s Differentiated Mechanism

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.

Nexavar is currently approved in more than 70 countries for liver cancer and in more than 80 countries for the treatment of patients with advanced kidney cancer. 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 cancers, including, lung cancer, breast cancer, colorectal cancer, lung cancer, ovarian cancer, and as an adjuvant therapy for kidney and liver cancer.

Important Safety Considerations For Patients Taking Nexavar

Based on the currently approved U.S. package insert for the treatment of patients with unresectable hepatocellular carcinoma, 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. Bleeding with a fatal outcome from any site was reported in 2.4% for Nexavar and 4% in placebo. The incidence of treatment-emergent cardiac ischemia/infarction was 2.7% for Nexavar vs. 1.3% for placebo. Most common adverse events reported with Nexavar in patients with unresectable HCC were diarrhea, fatigue, abdominal pain, weight loss, anorexia, nausea and hand-foot skin reaction. Grade 3/4 adverse events were 45% for Nexavar vs. 32% 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.

About Bayer HealthCare Pharmaceuticals Inc.

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 U.S., 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 Onyx Pharmaceuticals, Inc.

Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. The company, in collaboration with Bayer HealthCare Pharmaceuticals, Inc., is developing and marketing Nexavar(R) (sorafenib) tablets, a small molecule drug.

Forward Looking Statements

This news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup 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 which are available on the Bayer Web site at www.bayer.com. The company 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 results of the clinical development, safety, regulatory processes, commercialization efforts or commercial potential 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, 2008, 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(R) (sorafenib) tablets is a registered trademark of Bayer HealthCare Pharmaceuticals, Inc.

References

(1) British Medical Journal (BMJ), Liver cancer toll high in Japan, Adam Easton; 1999 June 5; 318(7197): 1510.

(2) 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 2009.

(3) El-Serag HB, Rudolf KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007; 132(7); 2557-2576.

(4) El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340:745-750

(5) Available at American Society of Clinical Oncology

(6) Ferlay J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5, Version 2.0. IARCPress, Lyon, 2004.

(7) Forner A, Hessheimer AJ, Isabel Real M, Bruix J. Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol. 2006; 60: 89- 98.

Source: Bayer HealthCare Pharmaceuticals

View drug information on Nexavar.

Overall prognosis for gallbladder cancer appears to be improving, although many patients still have incurable disease and poor survival rates, according to a report in the May issue ofArchives of Surgery, one of the JAMA/Archives journals.

An estimated 9,520 new cases of gallbladder or bile duct cancer were diagnosed in the United States in 2008, and approximately 3,340 of these patients will die of their disease, according to background information in the article. The disease affects women more frequently than men and surgical removal of diseased portions of the organ (resection) is the only curative treatment. However, many patients present to the clinician with advanced-stage disease and are not candidates for this procedure. “Gallbladder cancer is characterized by locally aggressive behavior, with early spread to regional lymph nodes and distant dissemination,” the authors write. “In addition, it recurs rapidly even after presumed curative resection.”

Ioannis T. Konstantinidis, M.D., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues identified 402 patients with gallbladder cancer at one university-affiliated tertiary care center between 1962 and 2008. Of these, 260 underwent surgical exploration at the same institution and were included in the data analysis. They were diagnosed during three periods: period A (1962 to 1979, 83 patients), period B (1980 to 1997, 105 patients) and period C (1998 to 2008, 72 patients).

Overall median (midpoint) survival improved from 3.5 months in period A to 6.5 months in period B and 12 months in period C. “The stage of disease at presentation affected the survival in all time periods (stage I, median survival not reached; stage II, 10.3 months; stage III, 4.7 months and stage IV, four months),” the authors write. “The survival of patients who presented with advanced-stage disease and who underwent palliative [treating symptoms only] procedures remained poor in all periods (A, 1.9 months; B, 3.9 months; and C, 3.6 months).”

Of the 260 cancer patients who had surgery to explore the extent of their disease, 151 (58.1 percent) underwent resection. Unresectable disease was found in eight patients and became less common over time (44.4 percent in periods A and B, 17.3 percent in period C).

Between January 1994 and March 2008, 6,881 laparoscopic cholecystectomies (procedures to remove gallstones) were performed at the same facility; 17 cases of gallbladder cancer were discovered incidentally during these procedures. “When gallbladder cancer is found incidentally during or after a cholecystectomy, aggressive resection should be performed either during the present operation or during a second operation,” the authors write. “In our series, 56 percent of patients who underwent re-exploration [a second surgery] were found to have residual disease. Patients underwent re-exploration at a median of 41 days, similar to other series. Increased T stage at cholecystectomy correlated with a higher frequency of residual disease.”

“Patients with gallbladder cancer continue to have a poor prognosis because many of the patients present with advanced disease,” the authors write. “Earlier detection coupled with an aggressive surgical approach leads to better outcomes. A better understanding of the molecular pathways contributing to the development of gallbladder cancer is needed to develop improved adjuvant therapies to increase overall survival.”

Arch Surg. 2009;144[5]:441-447.

Source
Archives of Surgery