WAYNE, N.J. and EMERYVILLE, Calif., Dec. 11 Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced results from two collaborative group-sponsored randomized, double-blind, placebo-controlled Phase 2 trials were presented at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS). The first of these studies evaluated NexavarŽ (sorafenib) tablets in combination with chemotherapy agent capecitabine and the second study evaluated Nexavar in combination with paclitaxel.
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"Onyx and Bayer are encouraged by these results as they suggest Nexavar may have potential as a combination therapy for advanced breast cancer patients in both the first and second-line setting," said Todd Yancey, M.D., senior vice president of clinical development at Onyx. "These findings, in particular the statistically significant results demonstrated with Nexavar in combination with capecitabine, are the basis for a registrational Phase 3 program that is expected to begin next year."
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Nexavar in Combination with Capecitabine
The randomized, double-blind, placebo-controlled Phase 2 study evaluated Nexavar in combination with the oral chemotherapeutic agent, capecitabine, in 229 patients. These patients had locally advanced or metastatic HER-2 negative breast cancer and had received no more than one prior chemotherapy in this setting.
Patients receiving capecitabine plus Nexavar had a 74 percent improvement in progression-free survival as compared to those who received chemotherapy alone. The increase in median progression-free survival of capecitabine plus Nexavar versus capecitabine plus placebo was statistically significant (median 6.4 months vs. 4.1 months, HR=.576, p=0.0006).
In a post-hoc, subgroup analysis of first-line patients, the combination of capecitabine plus Nexavar significantly extended progression-free survival to 7.6 months compared to 4.1 months (HR= 0.498, p=0.0022). In a second post-hoc subgroup analysis of second-line patients, the combination of Nexavar and capecitabine significantly extended progression-free survival 5.7 months compared to 4.1 months (HR=0.652, p=0.0339)
The primary endpoint of the study was progression-free survival. Secondary endpoints included overall survival, time-to-progression, and safety. Patients were randomized to receive 400 mg of oral Nexavar or matching placebo twice daily, in addition to 1000 mg/m2 of capecitabine.
Overall, treatment with capecitabine plus Nexavar did not result in any new side effects.
Common grade 3 treatment-related adverse events included hand-foot skin reaction (45%), diarrhea (5%), dyspnea (5%), neutropenia (4%) and mucositis (1%).
Top-line results from this study were previously presented at the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress.
Nexavar in Combination with Paclitaxel
The randomized, double-blind, placebo-controlled Phase 2 study evaluated Nexavar in combination with the chemotherapeutic agent, paclitaxel, in 237 patients. Patients were randomized to receive 400 mg of oral Nexavar or matching placebo twice daily, in addition to paclitaxel, given at 90 mg/m2 weekly for three weeks followed by one week of rest. These patients had locally recurrent or metastatic HER-2 negative breast cancer and had not received prior chemotherapy in this setting.
The primary endpoint of the study was progression-free survival (PFS). The PFS in patients receiving paclitaxel plus Nexavar compared to patients receiving paclitaxel plus placebo was 6.9 months vs. 5.6 months (HR=0.788, P=0.0857, one-sided).
Secondary endpoints included overall survival, time-to-progression, and safety. The difference in time-to-progression of paclitaxel plus Nexavar versus paclitaxel plus placebo was statistically significant, 8.1 months vs. 5.6 months (HR= 0.674, P=0.017 one-sided).
There were no new toxicities observed with the combination and adverse events were clinically manageable. Common grade 3 treatment-related adverse events included hand-foot skin reaction (30%), asthenia (7%), neutropenia (10%) and anemia (10%).
"The results from these two trials fuel our interest in exploring Nexavar in multiple settings through our comprehensive clinical program," said Dimitris Voliotis, vice president, Global Clinical Development Oncology, Bayer HealthCare. "Breast cancer is the second leading cause of cancer-related death in women, and we are committed to evaluating Nexavar's role in this often underserved patient population."
About the Nexavar Clinical Program in Breast Cancer
These two studies are part of a clinical development program known as TIES (Trials to Investigate the Effects of Sorafenib in Breast Cancer). Nexavar is being evaluated in collaboration with investigators and cooperative groups in four large randomized Phase 2 trials for patients with advanced breast cancer and in a variety of treatment settings. In addition to these two studies, there are two ongoing randomized Phase 2 studies, including a trial to evaluate Nexavar plus gemcitabine or capecitabine in the second-line setting following progression on bevacizumab, and a trial to evaluate Nexavar 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. (i)(ii)(iii)
Nexavar's Differentiated Mechanism
Nexavar, an oral anti-cancer therapy, is currently approved in more than 80 countries for liver cancer and in more than 90 countries 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 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, PDGFRB, KIT, FLT-3 and RET.
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, ovarian and colorectal cancer and as an adjuvant therapy for liver and kidney 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 and 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. In HCC patients, 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. In RCC patients, 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 adverse events greater than or equal to 20% related to Nexavar for both HCC and RCC were fatigue, weight loss, rash/desquamation, hand-foot skin reaction, alopecia, diarrhea, nausea, and abdominal pain. Grade 3/4 adverse events in HCC and RCC patients, respectively, were 45% for Nexavar vs. 32% for placebo and 38% for Nexavar and 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 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. Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, General Medicine, which includes Cardiology and Primary Care and Specialty Medicine, which includes Hematology, Oncology and Multiple Sclerosis. 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 NexavarŽ (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, a targeted alpha-folate inhibitor, is 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 also contains "forward-looking statements" of Onyx within the meaning of the federal securities laws. These forward-looking statements include without limitation, statements regarding timing, 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. 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.
NexavarŽ (sorafenib) tablets is a registered trademark of Bayer HealthCare Pharmaceuticals, Inc.
(i) American Cancer Society, 2007 Global Cancer Facts and Figures Report
(ii) American Cancer Society, 2009 Global Cancer Facts and Figures Report
(iii) Estimates of the cancer incidence and mortality in Europe in 2006, Annals of Oncology, 2007 Mar;18(3):581-92
SOURCE Onyx Pharmaceuticals, Inc.; Bayer HealthCare Pharmaceuticals Inc.
