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Positive Phase 2 Data for BAY 43-9006 in Patients With Advanced Kidney Cancer Announced
Analysis of the Phase II Randomized Discontinuation trial of BAY 43-9006 administered as a single agent showed activity in patients with advanced progressive kidney cancer. Of the 502 patients enrolled in the study, 202 were advanced kidney cancer patients, who had progressing disease upon study entry.
* The study met its primary endpoint in the kidney cancer population.
After 12 weeks of treatment with BAY 43-9006, 65 participants with
stable disease were randomized to receive placebo or BAY 43-9006. After
a subsequent 12-week treatment period, there was a statistically
significant higher percentage of participants whose disease did not
progress in the BAY 43-9006 group as compared to those who were
randomized to placebo.
* Based on investigator assessments, 70 percent of study participants with kidney cancer had tumor shrinkage or disease stabilization. In addition to the above 65 patients with stable disease who were randomized, 79 patients continued to receive BAY 43-9006 in the open-label portion of the trial.
* Based on investigator assessments the time to tumor progression was 169 days for the entire kidney cancer population (including placebo patients). Time to disease progression of approximately 60-90 days has been reported for control groups in other studies with similar patient populations.
The Phase II study was designed to determine if BAY 43-9006 contributes to tumor stabilization. The study was not prospectively designed to monitor tumor response rates (shrinkage of tumor) nor was it intended to be a registration study. As part of the development process, Bayer and Onyx established a charter for a retrospective independent radiologic review of the investigators' assessments of key tumor measurements. The independent review of time to progression (of the entire population including placebo patients) yielded results of 161 days, which was similar to the investigators' assessment. The independent review also confirmed that eight participants had formal partial responses per WHO criteria. The most commonly reported drug- related adverse events in the kidney cancer population included skin reactions such as hand-foot syndrome and rash, diarrhea, fatigue, weight loss and hypertension, which were shown to be manageable and reversible.
Based on these considerations, and the favorable enrollment progress of the ongoing Phase III trial, Bayer and Onyx will use the Phase II results to support the Phase III study for a potential filing for marketing approval. Subject to FDA approval, Bayer and Onyx would anticipate a US launch in 2006.
Phase III Summary
The multi-national, placebo-controlled Phase III study is expected to enroll over 800 patients with advanced kidney cancer. The primary endpoint of the study is overall survival with time-to-disease progression, overall response rate, and safety also being assessed.
The Phase III trial was initiated after a Special Protocol Assessment (SPA) was completed by the FDA in the fourth quarter of 2003. Approximately 100 international sites are actively participating in the study, and patient enrollment is proceeding well. The Phase III trial could serve as the basis for full marketing approval from the FDA if the trial meets the primary endpoint of overall survival.
Phase II Study Design
The BAY 43-9006 Phase II multi-center, randomized discontinuation trial used a study design consisting of two stages: a 12-week induction phase, followed by a 12 week randomization phase with a parallel BAY 43-9006 open- label phase for patients not randomized. During the first stage, all study participants received BAY 43-9006 orally at 400 mg twice a day. At the end of this first stage, investigators assessed the patients' tumors and directed patients to the next phase. Those patients whose tumor burden remained within plus or minus 25 percent of their pretreatment measurements were randomized to receive either BAY 43-9006 or placebo for an additional 12 week period. The primary endpoint of the study was the difference in the percent of patients (treated versus placebo) with stable disease at the second 12-week assessment. Additionally, those patients who had tumor shrinkage of more than 25 percent at the first 12-week evaluation continued treatment with open-label BAY 43- 9006. 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.
Source: Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc.