Bayer and Onyx announce pivotal Nexavar kidney cancer study published in NEJM
Bayer Pharmaceuticals Corporation (NYSE: BAY) and Onyx Pharmaceuticals, Inc. today announced that the New England Journal of Medicine has published their pivotal Phase III trial demonstrating that Nexavartermterm (sorafenibterm) tablets doubled median progression-free survival (PFS) in patients with advanced renal cell carcinomaterm (RCC), or kidney cancer. The data, as assessed by independent radiologic review, are from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) the largest randomized controlled trial ever conducted in advanced RCC. "Historically, patients with kidney cancer have had limited treatment options and there has been a particularly critical need for new therapies to help patients with advanced disease," said co-principal investigator Ronald Bukowski, M.D., Director of the Experimental Therapeutics Program of The Cleveland Clinic Taussig Cancer Center in Cleveland, OH. "This landmark study demonstrated the efficacy, tolerability and clinical benefit of Nexavar, which has rapidly become a valuable weapon against this devastating disease." Based on these data, Nexavar was granted U.S. Food and Drug Administration (FDA) approval for the treatment of patients with advanced RCC, or kidney cancer, on December 20, 2005. Since then, Nexavar has been approved in nearly 50 countries. "Nexavar was the first new drug approved for patients with advanced kidney cancer in over a decade," said Bill Bro, President and Chief Executive Officer of the Kidney Cancer Association (KCA). "With the advent of targeted therapies such as Nexavar, there has been remarkable change patients are experiencing improved outcomes without the toxic effects traditionally associated with chemotherapyterm."
Phase III Summary
More than 900 patients with advanced RCC were randomized one-to-one to receive either 400 mg Nexavar or placebo orally twice a day in this randomized, multi-national, placebo-controlled Phase III study. The endpoints of the study are overall survival (OS), PFS, overall response rate and safety. PFS measures the length of time that a patient lives without evident tumor growth or death. PFS doubled to a median of 5.5 months in patients receiving Nexavar compared to 2.8 months for patients receiving placebo (p < 0.001). This represented a 56% reduction in the risk of progression (hazard ratio 0.44; 95% CI, 0.35 to 0.55) for patients on Nexavar versus placebo. All patient subgroups examined benefited regardless of performance status or risk group, including patients who had not received conventional treatment with biologics, such as interleukin-2 or interferon-alpha. In May 2005, due to the clinical and statistical significance of the PFS data, the companies unblinded the trial and announced that patients who were receiving placebo were allowed to "cross over" to drug treatment. The first OS analysis conducted immediately before cross-over found a 39% improvement in OS for Nexavar patients (hazard ratio 0.72, p=0.018). A further OS analysis performed six months following cross over was based on 367 survival events (patient deaths) that had occurred by November 30, 2005. Results showed a continued trend toward improved survival, with a 23% reduction in the risk of death (19.3 months for Nexavar patients versus 15.9 months for placebo patients; hazard ratio 0.77, p=0.02), despite the fact that nearly half of placebo patients had "crossed over" to Nexavar. Patients continue to be followed and a final survival analysis will be available in the first half of 2007. The Phase III data published in NEJM have previously been communicated at international scientific congresses.