Nexavar in Combination with Chemotherapy Improves Progression-Free Survival in Patients with Advanced Breast Cancer in Phase 2 Study

WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., May 18, 2011 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals, Inc. and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced results from a Phase 2b trial evaluating Nexavar® (sorafenib) tablets in patients with locally advanced or metastatic breast cancer previously treated with a bevacizumab-containing regimen, which showed that Nexavar was associated with statistically significant improvements in progression-free survival (the primary endpoint of the study) and time-to-progression. The study evaluated Nexavar in combination with a chemotherapeutic agent, either gemcitabine or capecitabine. The data will be presented on June 6, 2011, at 11:45 a.m. during the oral abstract session at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL.

Clifford Hudis, M.D., Chief of the Breast Cancer Medicine Service and attending physician at the Memorial Sloan-Kettering Cancer Center, as well as Professor of Medicine at Weill Cornell Medical College, reported that patients receiving Nexavar in addition to standard chemotherapy agents obtained a progression-free survival benefit with median of 3.4 months to progression versus 2.7 (HR=0.65, one-sided p-value=0.01). Time-to-progression was similarly improved from a median of 3.6 months from 2.7 (HR=0.64; one-sided p-value=0.009) in this pre-treated population.

"These results demonstrate the importance of continuing to evaluate antiangiogenic compounds in breast cancer, and their study should remain a high priority for the research community," said Dr. Hudis.

"These data are similar to those observed in our previous Phase 2 trial evaluating Nexavar in combination with capecitabine," said Ted W. Love, M.D., Executive Vice President and Head of Research and Development and Technical Operations for Onyx Pharmaceuticals.  "Onyx and Bayer are continuing to explore Nexavar's potential utility in breast cancer through a Phase 3 trial evaluating Nexavar in combination with capecitabine in advanced breast cancer in the RESILIENCE (Phase 3 TRial Comparing CapecitabinE in Combination with SorafenIb or PLacebo for Treatment of Locally Advanced or MetastatIc HER2–Negative Breast CancEr) trial."

The safety and tolerability profile of the combination was consistent with the previous experience. The most commonly reported treatment-emergent Grade 3/4 adverse events were hand-foot skin reaction (39 percent), neutropenia (21 percent) and stomatitis (10 percent).

Phase 2b Trial Design

This Phase 2b randomized, double-blind, placebo-controlled trial evaluated Nexavar in combination with chemotherapeutic agents, gemcitabine (1000 mg/m2) or capecitabine (1000 mg/m2) in 160 patients with locally advanced or metastatic HER-2 negative breast cancer who were previously treated with a bevacizumab-containing regimen. Patients were randomized to receive 400 mg of oral Nexavar or matching placebo twice daily, in addition to chemotherapeutic agents – gemcitabine or capecitabine. The primary endpoint was progression-free survival, and secondary endpoints included overall survival, time-to-progression and safety.

"We continue to explore the utility of Nexavar as a potential treatment option for breast cancer patients in variety of settings, including in the ongoing RESILIENCE Phase 3 trial," said Dr. Dimitris Voliotis, Vice President, Global Clinical Development Oncology, Bayer HealthCare.  "As the second leading cause of cancer-related death in women, there is still an unmet need for treatments for these advanced patients.  We remain committed to evaluating Nexavar in this patient population."

About the RESILIENCE Phase 3 Breast Cancer Trial

The RESILIENCE trial is a company-sponsored, randomized, double-blind, placebo-controlled Phase 3 study planned to enroll approximately 500 patients in more than 20 countries, including the United States, Brazil, Japan and Australia. The study will evaluate Nexavar in combination with capecitabine in patients with locally advanced or metastatic HER-2 negative breast cancer who are resistant to or have failed prior taxane and an anthracycline or for whom further anthracycline is not indicated. The primary endpoint of the study is progression-free survival. Secondary endpoints include overall survival, time to progression, and safety.

About the Nexavar Clinical Program in Breast Cancer

This study is part of a company-supported clinical development program known as TIES (Trials to Investigate the Effects of Sorafenib in Breast Cancer), where sorafenib is being evaluated in four investigator/cooperative group-sponsored Phase 2 trials for patients with advanced breast cancer and in a variety of treatment settings. The remaining ongoing trial under this program is evaluating sorafenib plus docetaxel and/or letrozole in the first-line setting.

About Breast Cancer

Breast cancer was the most commonly diagnosed cancer among women worldwide in 2007-2008 (approximately 1.3 million cases), and the second leading cause of cancer-related death among women (approximately 465,000 deaths). It is the most commonly diagnosed cancer among women in the United States (1 in 4 cancer diagnoses is breast cancer). There are approximately 200,000 new cases of breast cancer in the United States and 430,000 in Europe each year. More than 40,000 women in the United States and more than 130,000 in Europe die of breast cancer each year. (l)(ll)(lll)

About Nexavar

Nexavar is approved in the U.S. for the treatment of patients with unresectable liver cancer and for the treatment of patients with advanced kidney cancer. Nexavar inhibits both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to inhibit members of two classes of kinases thought 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.

Nexavar is currently approved in more than 100 countries.

Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators.

Important Safety Considerations For Patients Taking Nexavar

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 breast-feeding 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.

Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Caution is recommended when administering Nexavar with compounds that are metabolized/eliminated predominantly by the UGT1A9 pathway, UGT1A1 pathway (eg, irinotecan), doxorubicin, docetaxel, fluorouracil, and substrates of CYP2B6 and CYP2C8, and CYP3A4 inducers.

Concomitant use of carboplatin and paclitaxel with sorafenib resulted in an increase in paclitaxel exposure and an increase in Nexavar exposure. Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes. 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 postapproval 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 www.nexavar.com or call 1.866.NEXAVAR (1.866.639.2827).

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, Diabetes Care, and Pharmaceuticals divisions. As a specialty pharmaceutical company, Bayer HealthCare Pharmaceuticals provides products for Diagnostic Imaging, 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.

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® (sorafenib) tablets, a small molecule drug that is currently approved for the treatment of liver cancer and advanced kidney cancer. Additionally, Nexavar is being investigated in several ongoing trials in a variety of tumor types. Beyond Nexavar, Onyx has established a development pipeline of anticancer compounds at various stages of clinical testing, including carfilzomib, a next generation proteasome inhibitor, that is currently being evaluated in multiple clinical trials for the treatment of patients with relapsed or relapsed/refractory multiple myeloma and solid tumors. ONX 0801, an alpha-folate receptor targeted inhibitor of the thymidylate synthase, and ONX 0912, an oral proteasome inhibitor, are currently in Phase 1 testing. For more information about Onyx, visit the company's website at www.onyx-pharm.com.

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 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, 2010, 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.

(l) American Cancer Society, 2007 Global Cancer Facts and Figures Report

(ll) American Cancer Society, 2009 Global Cancer Facts and Figures Report

(lll) Estimates of the cancer incidence and mortality in Europe in 2006, Annals of Oncology, 2007 Mar;18(3):581-92

SOURCE Bayer HealthCare Pharmaceuticals, Inc.; Onyx Pharmaceuticals, Inc.