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Deno...

Amgen (Nasdaq: AMGN) today announced that a pivotal, Phase 3, head-to-head trial evaluating denosumab versus Zometa® (zoledronic acid) in the treatment of bone metastases in 1,901 men with advanced prostate cancer met its primary and secondary endpoints. Denosumab demonstrated superiority over Zometa for both delaying the time to the first on-study skeletal related event (SRE) (fracture, radiation to bone, surgery to bone or spinal cord compression) (hazard ratio 0.82, 95 percent CI: 0.71, 0.95), and reducing the rate of multiple SREs (hazard ratio 0.82, 95 percent CI: 0.71, 0.94). Both results were statistically significant.

Overall rates of adverse events and serious adverse events, including infections, were generally similar between the two arms. Osteonecrosis of the jaw was infrequent (22 patients receiving denosumab as compared with 12 patients receiving Zometa) and there was no statistically significant difference between treatment arms. As with previous studies in advanced cancer patients, hypocalcemia was more frequent in the denosumab arm. Both overall survival and the time to cancer progression were balanced between treatment arms.

"These Phase 3 results demonstrate the ability of denosumab to delay bony complications in patients suffering from metastatic prostate cancer," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "Denosumab has shown remarkable consistency in reducing the serious complications of bone metastases. Today's results greatly enhance our understanding of the efficacy of denosumab in multiple different tumor types."

This study is the final of three pivotal trials in a total of over 5,700 advanced cancer patients investigating the potential of denosumab to treat bone metastases. Results from the previous two trials were presented in September 2009. These three studies will form the basis of the clinical evidence package for denosumab in advanced cancer, which will be submitted to regulatory authorities later this year.

Full efficacy and safety data for the prostate cancer study will be submitted to the American Society for Clinical Oncology, for possible presentation at their meeting in early June. Additionally, results are expected in the second half of the year from a study investigating whether denosumab may prolong bone metastasis-free survival in prostate cancer patients.

Study Design

This study was an international, Phase 3, randomized, double-blind study comparing denosumab with Zometa in the treatment of bone metastases in patients with advanced prostate cancer. Patients enrolled in the study were randomized in a one-to-one ratio to receive either 120 mg of denosumab subcutaneously every four weeks (Q4W) or Zometa administered intravenously as at least a 15 minute infusion at a dose of 4 mg every four weeks as per the labeled instructions. The study consisted of 1,901 patients, mean age of 71, who have bone metastases from hormone-refractory prostate cancer.

In clinical trials testing new medications for bone metastases, treatment success has been measured by whether the bone complications, or SREs, caused by the bone metastases are reduced or delayed. The primary and secondary endpoints of the denosumab bone metastases studies use a composite endpoint of four SREs - fracture, radiation to bone, surgery to bone, and spinal cord compression - to measure the effectiveness of denosumab versus Zometa.

The primary endpoint was to evaluate if denosumab is non-inferior to Zometa with respect to the first on-study SRE in patients with advanced prostate cancer and bone metastases. Secondary endpoints were to evaluate if denosumab was superior to Zometa with respect to the first on-study SRE, as well as first-and-subsequent on-study SREs, and to assess the safety and tolerability of denosumab compared with Zometa.