Encouraging interim results on BAY 43-9006 in advanced kidney cancer


Data show durable responses in addition to tumor shrinkage and disease stabilization

New Orleans, LA June 5, 2004 Bayer Pharmaceuticals Corporation (NYSE: BAY) and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced encouraging new interim results from a Phase II clinical trial of BAY 43-9006 used as a single agent in patients with advanced renal cell carcinoma (RCC), or kidney cancer. The results were presented at the annual meeting of the American Society of Clinical Oncology in New Orleans.

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.

"In this study, the use of BAY 43-9006 in patients with renal cell carcinoma has resulted in a high level of durable disease stabilization or tumor shrinkage," said lead investigator Mark Ratain, M.D., Professor of Medicine and Associate Director for Clinical Sciences, Cancer Research Center, University of Chicago, USA. "As we continue to evaluate BAY 43-9006, I am excited about the potential it may offer in the fight against this form of kidney cancer."

The data included tumor response for 89 participants (of 106 total RCC patients) who were assessed at 12 weeks, as well as duration of response data for 37 of these participants who experienced tumor shrinkage of greater than 25 percent. Thirteen of the participants had their tumors shrink by at least 50 percent at the 12-week assessment. Nine patients were confirmed to have this degree of tumor response by subsequent scans conducted at least six weeks later. Thirty-eight participants had disease stabilization and were randomized. The remaining 31 (of 106) participants had disease progression or were discontinued from the study for other reasons.

The entire group of 37 patients who had tumor shrinkage, and continued to receive BAY 43-9006 in the open-label phase of the study, had an estimated median time to tumor progression (TTP) of 48 weeks based on investigator assessment. Of these, 88 percent were progression free at six months. These investigator-reported data, including the confirmatory radiology scans needed to define response rates, are subject to a final independent radiologic review, which will be completed by the sponsor at the conclusion of the study.

Over 85 percent of the study participants with RCC had tumors that progressed despite at least one prior systemic treatment, and all patients had progressive disease on study entry. The RCC participants were part of a larger study population consisting of 484 treated patients with advanced refractory solid tumors of multiple types. Safety data were collected for all tumor types. In the study, the most commonly reported drug-related events include mild-to-moderate hand-foot syndrome, rash, diarrhea, and hypertension, which were shown to be manageable and reversible.

"The analysis of the RCC patient experience in this Phase II study is expected to be complete in the second half of the year," said Susan Kelley, M.D., vice president, Oncology, Bayer Pharmaceuticals Corporation. "We remain encouraged by these early findings, and are very pleased that enrollment in the ongoing worldwide Phase III RCC study is proceeding well, with virtually all trial sites open and actively accepting patients."

Phase II Study Design
The BAY 43-9006 Phase II multi-center, randomized discontinuation trial, which enrolled more than 200 RCC patients, uses a study design that consists of two stages: a 12-week induction phase followed by a randomization phase and a parallel BAY 43-9006 open-label phase. During the first stage, all study participants received BAY 43-9006 orally at 400 mg twice a day. Subsequently, those patients whose tumor burden was within 25 percent of their pretreatment measurements were randomized to either BAY 43-9006 or placebo for another 12 weeks of treatment. At its conclusion, the codes will be broken on the randomized patients to evaluate possible evidence of the compound's contribution to the disease stabilization of these patients. Additionally, those patients who had tumor shrinkage of more than 25 percent at the week 12 evaluation continued to be treated with open-label BAY 43-9006 after the initial 12-week stage. Patients who had tumor growth of 25 percent or more were discontinued from the study.

About BAY 43-9006
BAY 43-9006, a novel investigational drug candidate, 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 Data
Additional BAY 43-9006 data being presented at this year's ASCO meeting include:

  • Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. Keith T. Flaherty, MD. Abstract #7507 (Oral Presentation)
  • BAY 43-9006 in patients with advanced melanoma: The Royal Marsden experience. Tanya Ahmad, MRCP. Abstract #7506 (Oral Presentation)
  • A phase I/II trial of BAY 43-9006 and gemcitabine in advanced solid tumors and in advanced pancreatic cancer. Lillian L. Siu, MD. Abstract #3059 (Poster #M9)
  • Results of a phase I trial of BAY 43-9006 in combination with doxorubicin in patients with refractory solid tumors. Heike Richly, MD. Abstract #3049 (Poster #L10)
  • A randomized phase I clinical and biologic study of two schedules of BAY 43-9006 in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): A National Cancer Institute of Cancer Clinical Trials Group Study. Michael Crump, MD. Abstract #6611 (Poster # L11)
  • Pharmacodynamic study of the RAF kinase inhibitor BAY 43-9006: Mechanisms of hypertension. Maria Luisa Veronese, MD. Abstract #2035 (Poster #25)
  • Results of a phase I trial of BAY 43-9006 in combination with oxaliplatin in patients with refractory solid tumors. Petra Kupsch, MD. Abstract #3056 (Poster #M6)

Kidney Cancer
Renal cell carcinoma is the most common form of kidney cancer. Nearly 190,000 people worldwide are diagnosed (about 31,000 Americans) with renal cell carcinoma each year, and more than 91,000 of them die (about 12,000 Americans) from the disease annually. For more information on renal cell carcinoma, visit the Kidney Cancer Association (KCA) web site at: www.kidneycancerassociation.org.

Source: Eurekalert & others

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