Phase 3 MISSION trial of Nexavar (sorafenib) in Patients with Non-Small Cell Lung Cancer Did Not Meet Primary Endpoint of Improving Overall Survival

WAYNE, N.J. and SOUTH SAN FRANCISCO, Calif., May 22, 2012 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced that a Phase 3 trial evaluating Nexavar^® (sorafenib) tablets in patients with advanced relapsed or refractory non-squamous non-small cell lung cancer (NSCLC) whose disease progressed after two or three previous treatments, did not meet its primary endpoint of improving overall survival.  An improvement in the secondary endpoint of progression-free survival (PFS) was observed.

The study compared Nexavar plus best supportive care to placebo plus best supportive care. The safety and tolerability data were generally as expected.  The data will be presented at an upcoming scientific meeting.

"While we are disappointed that the primary endpoint was not met, we believe the study results will advance the scientific knowledge in lung cancer," said Dr. Dimitris Voliotis, Vice President, Global Clinical Development Oncology, Bayer HealthCare.

Phase 3 Trial Design

The MISSION (Monotherapy admInistration of Sorafenib in patientS wIth nOn-small cell luNg cancer) trial is an international multicenter study that randomized 703 patients with advanced relapsed or refractory non-squamous NSCLC whose disease progressed after two or three previous treatments. Patients were randomized to receive either Nexavar as single agent or placebo. In both study arms, best supportive care was provided. The primary endpoint of the trial was overall survival, and secondary endpoints included progression-free survival, disease control rate, overall response rate, time to progression and quality of life.

The study was conducted at more than 150 sites in North America, South America, Europe, Africa and the Asia-Pacific region, including Japan.

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the most common cancer worldwide, with approximately 1.2 million new cases annually. There are approximately 226,000 new cases of lung cancer in the United States and approximately 417,000 in Europe each year.[i]

NSCLC accounts for 85-90 percent of lung cancer[ii] and is a disease in which malignant (cancer) cells form in the tissues of the lung.  It is characterized by several types of lung cancers, each of which grow and spread in different ways, including: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma.

About Nexavar (sorafenib)
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 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 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, 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 www.onyx.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, 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.

[i] http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2012

[ii] http://www.cancer.org/Cancer/LungCancer-Non-SmallCell/DetailedGuide/non-small-cell-lung-cancer-what-is-non-small-cell-lung-cancer

SOURCE Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc.