BAY 43-9006, a novel RAF kinase and VEGFR inhibitor under investigation for the prevention of tumor growth, combines two anticancer activities: inhibition of tumor cell proliferation and tumor angiogenesis.
The evaluation included 35 study participants in the Phase I/II study, the majority of whom had advanced metastatic melanoma. Eighty three percent of study participants treated with the combination of BAY 43-9006 plus carboplatin and paclitaxel were observed to have tumor shrinkage (40 percent) or disease stabilization (43 percent) while on study treatments. Of the 35 study participants, fourteen participants (40 percent) had tumor shrinkage of 50 percent or greater, all of which lasted for six months or more. At the time of this analysis, only three of these participants had disease progression at 10 to 12 months. An additional 15 participants (43 percent) had disease stabilization. Six participants had disease progression or exited the trial for other reasons. For all study participants, estimated median time to disease progression (TTP) was 10 months based on investigator assessment. Trial data are subject to final independent review at the end of the study.
"These are encouraging results as a majority of these patients had metastases to visceral organs. Despite the severity of their disease, we observed 40 percent of the patients as having partial responses for a prolonged period of time," said lead investigator Keith T. Flaherty, M.D., instructor of medicine, Abramson Cancer Center, University of Pennsylvania. "In a disease with limited treatment options, these preliminary findings are encouraging."
According to the study data, this combination demonstrated activity that was not solely dependent on a BRAF gene mutation to activate the Ras pathway. BRAF gene mutations, of which V599E is the most common form, are thought to occur in about two-thirds of malignant melanoma tumors.
"The data from this study using the combination of BAY 43-9006 with carboplatin and paclitaxel appeared more encouraging than that obtained when BAY 43-9006 was administered as a single agent in other clinical experience," said Susan Kelley, M.D., vice president, Oncology, Bayer Pharmaceuticals Corporation. "Bayer and Onyx are pleased with the data generated to date and are planning a pivotal trial with this combination."
In the study, the non-hematologic side effects observed with the combination were consistent with those known to occur with each agent delivered alone. The most common included hand-foot syndrome, infection, vomiting, and rash. No pharmacokinetic interaction between BAY 43-9006 and paclitaxel or carboplatin was reported.
Phase l/Phase II Study Design
Initially designed to evaluate the safety and preliminary efficacy of BAY 43-9006 administered in combination with carboplatin and paclitaxel, the Phase I/II trial was expanded to evaluate the effectiveness of the regimen in patients with advanced melanoma patients once the safety of the combination was observed.
About BAY 43-9006
BAY 43-9006, a novel investigational drug candidate, has demonstrated both anti-proliferative and anti-angiogenic properties – two important anticancer activities. In preclinical models, BAY 43-9006 inhibited tumor cell proliferation by targeting the RAF/MEK/ERK signaling pathway at the level of RAF kinase. BAY 43-9006 also exerted an antiangiogenic effect by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR and their associated signaling cascades.
For more information on BAY 43-9006 clinical trials, visit www.clinicaltrials.gov.
Additional BAY 43-9006 ASCO Melanoma Data
Data from a separate study of BAY 43-9006 administered as a single agent in patients with malignant melanoma were also presented at the meeting (abstract #7506). Tanya Ahmad, MRCP of The Royal Marsden Hospital, London, reported that BAY 43-9006 had modest anti-tumor activity when delivered as monotherapy to patients with advanced malignant melanoma. It was concluded from these preliminary data that BAY 43-9006 delivered in combination with standard chemotherapeutics was a more promising therapeutic approach for patients with this disease. The Royal Marsden currently has a study underway combining BAY 43-9006 and the chemotherapeutic agent dacarbazine for treatment of patients with malignant melanoma.
Melanoma
Cancer of the skin (nonmelanoma and melanoma skin cancers combined) is the most common type of cancer, accounting for more than 50 percent of all cancers. Melanoma accounts for about 4 percent of skin cancer cases but causes about 79 percent of skin cancer deaths. About 132,000 people worldwide (about 55,000 Americans) are diagnosed with melanoma each year, and more than 37,000 (about 8,000 Americans) of them die from the disease annually. Once the disease becomes metastatic, it is rapidly fatal due to the lack of an effective therapy. For more information on melanoma, visit the Melanoma International Foundation (MIF) web site at: www.melanomainternational.org.
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 BAY 43 9006 with Bayer Pharmaceuticals Corporation. For more information about Onyx's pipeline and activities, visit the company's web site at www.onyx-pharm.com.
About Bayer Pharmaceuticals Corporation
Bayer Pharmaceuticals Corporation (www.bayerpharma.com) is part of the worldwide operations of Bayer HealthCare AG, a subgroup of Bayer AG.
Bayer HealthCare, with sales of approximately 8.9 billion Euro in 2003, is one of the world's leading, innovative companies in the health care and medical products industry.
The company combines the global activities of the divisions Animal Health, Biological Products, Consumer Care, Diagnostics and Pharmaceuticals. Bayer HealthCare employs 34,600 people worldwide.
Our aim is to discover and manufacture innovative products that will improve human and animal health worldwide. Our 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 BAY43-9006. 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 Onyx's Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 15, 2004 under the heading "Additional Business Risks" 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.
Additional Contact Information:
Mark Bennett
Bayer Pharmaceuticals Corporation
203-812-2160
203-314-5556 (onsite at ASCO)
Helmut Schaefers
Bayer HealthCare Communications
49-214-305-8308
Julie Wood
Onyx Pharmaceuticals, Inc.
510-262-8757
925-247-4330 (onsite at ASCO)
Eileen Crowley
GCI Group
212-537-8116
646-732-6855 (onsite at ASCO)