VEGFR2 x FLT3 x VEGFR

WAYNE, N.J., SOUTH SAN FRANCISCO, Calif. and TOKYO, July 23, 2012 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX), and Astellas Pharma Inc. (TSE: 4503) today announced that a Phase 3 trial evaluating the efficacy and safety of the addition of Tarceva® (erlotinib) tablets to Nexavar® (sorafenib) tablets did not improve overall survival for patients with unresectable hepatocellular carcinoma (HCC) vs. Nexavar alone. The SEARCH (Sorafenib and Erlotinib, a rAndomized tRial protoCol for the treatment of patients with Hepatocellular carcinoma) trial compared Nexavar in combination with Tarceva to Nexavar alone. The safety and tolerability of the treatment combination were generally as expected based upon experience and use of the two products alone and there were no new or unexpected toxicities or changes to the respective product safety profiles observed. Data from this study will be presented at an upcoming scientific meeting. Nexavar is jointly developed by Bayer and Onyx. Tarceva is jointly marketed by Astellas and Genentech, a member of the Roche Group. "The data from SEARCH showed that the addition of Tarceva to Nexavar did not provide additional benefit to patients with unresectable HCC," said Dr. Dimitris Voliotis, Vice President, Global Clinical Development Oncology, Bayer HealthCare. "The results of this trial confirm the efficacy and safety pro Nexavar in the treatment of unresectable liver cancer." About the Phase 3 Study The SEARCH trial was an international multicenter placebo-controlled Phase 3 study that randomized 720 patients with advanced liver cancer. The study examined whether the addition of Tarceva to Nexavar prolongs survival as compared to Nexavar alone in patients with unresectable HCC. The primary endpoint of the study was overall survival (OS) and the secondary endpoints were safety, time to radiographic progression (TTP), disease control rate (DCR) and patient-reported outcome. Patients were randomized to receive either 400 mg of Nexavar twice daily and 150 mg of Tarceva once daily or 400 mg of Nexavar twice daily with matching placebo. About Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is responsible for approximately 90 percent of the primary liver cancers in adults.[1][2] Liver cancer is the seventh most common cancer in the world and the third leading cause of cancer-related deaths globally.[3][4] About Nexavar (sorafenib) Tablets Nexavar is approved in the U.S. for the treatment of patients with unresectable hepatocellular carcinoma and for the treatment of patients with advanced renal cell carcinoma. Nexavar is thought to inhibit both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to inhibit multiple kinases thought to be involved in both cell proliferation (growth) and angiogenesis (blood supply) two important processes that enable cancer growth. These kinases include Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. Nexavar is currently approved in more than 100 countries. Nexavar is also being evaluated by Bayer and Onyx, international study groups, government agencies and individual investigators in a range of cancers. Important Safety Considerations For Nexavar (sorafenib) Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breastfeeding while receiving Nexavar. Cardiac ischemia and/or myocardial infarction may occur. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or myocardial infarction. Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar. Uncommon but serious adverse reactions, including keratoacanthomas/squamous cell cancer of the skin and Stevens-Johnson Syndrome, have been reported in clinical trials. An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar. Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required. Hand-foot skin reaction and rash are common and management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of Nexavar should be considered. Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures. Nexavar can prolong the QT/QTc interval and increase the risk for ventricular arrhythmias. Avoid use in patients with congenital long QT syndrome and monitor patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Monitor patients taking concomitant warfarin regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Avoid concomitant use of strong CYP3A4 inducers, when possible, because inducers can decrease the systemic exposure of sorafenib. Nexavar exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied. Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% vs 32%. Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in advanced RCC, respectively, were: diarrhea (43% vs 13%), rash/desquamation (40% vs 16%), fatigue (37% vs 28%), hand-foot skin reaction (30% vs 7%), alopecia (27% vs 3%),and nausea (23% vs 19%). Grade 3/4 adverse reactions were 38% vs 28%. During post approval use of Nexavar, the following adverse drug reactions have been identified: angioedema and drug-induced hepatitis, including reports of hepatic failure and death. For information about Nexavar including U.S. Nexavar prescribing information, visit or call 1.866.NEXAVAR (1.866.639.2827). About Tarceva Maintenance Therapy and Second- or Third-Line Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC): Tarceva is prescribed for patients with advanced-stage non-small cell lung cancer (NSCLC) whose cancer has not spread or grown after initial treatment with certain types of chemotherapy. (Maintenance treatment) Tarceva is prescribed for patients with advanced-stage non-small cell lung cancer (NSCLC) whose cancer has spread or grown after receiving at least 1 chemotherapy regimen. (2nd/3rd-line treatment) Tarceva is not meant to be used at the same time as certain types of chemotherapy for advanced NSCLC. Advanced Pancreatic Cancer: Tarceva in combination with gemcitabine is prescribed for patients with advanced-stage pancreatic cancer whose cancer has spread, grown, or cannot be surgically removed and who have not received previous chemotherapy. Important Safety Information for Tarceva Serious side effects (including deaths) in patients taking Tarceva include Interstitial Lung Disease (ILD)-like events; liver and/or kidney problems; gastrointestinal (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); serious skin conditions; and bleeding events including gastrointestinal and non-gastrointestinal bleeding when taking warfarin or non-steroidal anti-inflammatory drugs (NSAIDs). Patients taking Tarceva plus gemcitabine were more likely to experience bleeding and clotting problems such as heart attack or stroke. Eye irritation and damage to the cornea have been reported in patients taking Tarceva. Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva. Patients should call their doctor right away if they have these signs or symptoms: new or worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, or vomiting; new or worsening shortness of breath or cough; or eye irritation. Rash and diarrhea were the most common side effects associated with Tarceva in the non-small cell lung cancer clinical studies. Fatigue, rash, nausea, loss of appetite, and diarrhea were the most common side effects associated with Tarceva plus gemcitabine therapy in the advanced pancreatic cancer clinical study. For full prescribing information, please call 1-877-TARCEVA or visit . Tarceva is a trademark of OSI Pharmaceuticals, LLC, Farmingdale, NY 11735, USA, an affiliate of Astellas Pharma US, Inc. About Bayer HealthCare Pharmaceuticals Inc. Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Medical Care, and Pharmaceuticals divisions. As a specialty pharmaceutical company, Bayer HealthCare provides products for General Medicine, Hematology, Neurology, Oncology and Women's Healthcare. 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 Based in South San Francisco, California, Onyx Pharmaceuticals, Inc. is a global biopharmaceutical company engaged in the development and commercialization of innovative therapies for improving the lives of people with cancer. The company is focused on developing novel medicines that target key molecular pathways. For more information about Onyx, visit the company's website at . About Astellas Astellas Pharma Inc., located in Tokyo, Japan, is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. Astellas has approximately 17,000 employees worldwide. The organization is committed to becoming a global category leader in Urology, Immunology (including Transplantation) and Infectious Diseases, Oncology, Neuroscience and DM Complications and Kidney Diseases. For more information on Astellas Pharma Inc., please visit the company website at . 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 . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. This news release contains "forward-looking statements" of Onyx within the meaning of the federal securities laws. These forward-looking statements include without limitation, statements regarding the progress and 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, including risks related to the development and commercialization of pharmaceutical products. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Reference should be made to Onyx's Annual Report on Form 10-K for the year ended December 31, 2011, 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 HealthCare Pharmaceuticals, Inc. [1] El-Serag HB. Hepatocellular Carcinoma. N Engl J Med. 2011;365:1118-27. [2] Available at American Society of Clinical Oncology: [3] GLOBOCAN 2008. Country Fast Stat. Available at: . [4] 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 and Onyx Pharmaceuticals, Inc.

Renal Cell Carcinoma Approval Received in Mexico WEST HAVEN, Conn. and EMERYVILLE, Calif., April 28 /PRNewswire-FirstCall/ -- Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc. today announced that they have received a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) for Nexavar(R) (sorafenib) 200 mg film-coated tablets for the treatment of patients with advanced renal cell carcinoma (RCC), or kidney cancer, who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy. This positive CHMP opinion will be elevated to the European Commission where a positive ruling could lead to Marketing Authorization for all countries in the European Union in the second half of 2006. The companies also announced the approval of Nexavar (sorafenib) tablets by the Mexican Ministry of Health for the treatment of patients with advanced renal cell carcinoma (RCC), or kidney cancer. Nexavar, which has been shown to double progression-free survival in patients with advanced RCC, will be marketed by Bayer in the EU as well as in Mexico. "This positive opinion from the CHMP -- received earlier than originally anticipated -- marks another important milestone, bringing us one step closer to the global launch of Nexavar," said Dr. Gunnar Riemann, Head of Bayer HealthCare's Pharmaceuticals Division. "With the recent approval by the Mexican Ministry of Health, there are now three countries that have approved Nexavar for the treatment of kidney cancer." Nexavar was approved by the U.S. Food and Drug Administration (FDA) in December 2005 and in March 2006 in Switzerland. In addition, Bayer has completed filings in several countries, including Australia, Brazil, Canada, and Turkey. About Nexavar Nexavar is the first oral multi-kinase inhibitor that targets both the tumor cell and tumor vasculature. In preclinical models, Nexavar targeted members of two classes of kinases known to be involved in both tumor cell proliferation (tumor growth) and tumor angiogenesis (tumor blood supply) -- two important cancer growth activities. These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-B, KIT, and FLT-3. Nexavar has been studied in more than 20 tumor types and in nearly 8,000 clinical trial patients. Nexavar is currently in Phase III clinical trials for the treatment of advanced hepatocellular carcinoma (HCC), or liver cancer, and metastatic melanoma, or skin cancer. A Phase III clinical trial in non-small cell lung cancer (NSCLC) was initiated in February 2006. In addition to company-sponsored trials, there are a variety of Nexavar studies being sponsored by government agencies, cooperative groups and individual investigators. Important Safety Considerations for U.S. Patients Taking Nexavar Based on the current, 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 or call 1.866.NEXAVAR (1.866.639.2827). Bayer/Onyx Co-Development Nexavar is being co-developed by Bayer and Onyx. The co-development collaboration calls for Onyx to fund 50 percent of the development and marketing costs for Nexavar worldwide, except in Japan. In return, Onyx has a 50/50 profit share in the United States, where the companies co-promote the product. In all other countries (except Japan) Bayer has exclusive marketing rights and Onyx's profit share is slightly less than 50 percent. In Japan, Bayer will fund product development and Onyx will receive a royalty. About Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals, Inc. is engaged in the development of novel cancer therapies that target the molecular basis of cancer. With its collaborators, the company is developing small molecule drugs, including Nexavar with Bayer Pharmaceuticals Corporation. For more information about Onyx's pipeline and activities, visit the company's web site at: . About Bayer Pharmaceuticals Corporation Bayer Pharmaceuticals Corporation ( ) is part of the worldwide operations of Bayer HealthCare AG, a subsidiary of Bayer AG. Bayer HealthCare AG, with sales of approximately 9.4 billion Euros in 2005, is one of the world's leading, innovative companies in the healthcare and medical products industry. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care, Diagnostics and Pharmaceuticals divisions. Bayer Pharmaceuticals Corporation is part of the new Global Pharmaceutical Division, established January 1, 2006, which consists of the former Biological Products and Pharmaceutical Division and now comprises three business units: Hematology/Cardiology; Oncology and Primary Care. Bayer HealthCare AG employed 33,800 people worldwide in 2005. Bayer HealthCare AG's aim is to discover and manufacture innovative products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating disease. 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(R) (sorafenib) tablets is a registered trademark of Bayer Pharmaceuticals Corporation. Bayer Pharmaceuticals Corporation; Onyx Pharmaceuticals, Inc. CONTACT: Mark Bennett, +1-203-812-2160, or Dr Michael Diehl,+49-214-30-58532, both of Bayer HealthCare; or Julie Wood of OnyxPharmaceuticals, Inc., +1-510-597-6505; or Geoff Curtis of GCI Group,+1-312-229-8702 Web site: