Phase 3 trial demonstrates superiority of Amgen's denosumab over Zometa in preventing SREs

Amgen (Nasdaq: AMGN) today announced detailed results from a Phase 3, head-to-head trial which compared the efficacy and safety of denosumab versus Zometa® (zoledronic acid) in 1,901 patients with hormone-refractory prostate cancer and bone metastases. The study met its primary and secondary endpoints and demonstrated denosumab's superiority over Zometa in delaying or preventing skeletal related events (SREs). These statistically significant results will be presented in an oral session on June 6, 2010 at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting in Chicago (Late Breaking Abstract Number #LBA4507).  

In patients with skeletal metastases, the growing cancer cells weaken and destroy the bone around the tumor. This can result in a number of serious complications, collectively called SREs, comprising fracture, radiation to bone, surgery to bone or spinal cord compression. All can be serious complications for advanced cancer patients.

In this study, denosumab was superior to Zometa in significantly delaying the time to first on-study SRE (hazard ratio 0.82, 95 percent CI: 0.71, 0.95; P = 0.008) with a median time to first on-study SRE of 20.7 months versus 17.1 months for Zometa. Denosumab was also superior to Zometa in significantly delaying the development of multiple SREs (time to first and subsequent on-study SRE).

"Bone metastases are debilitating complications of prostate cancer, affecting up to 75 percent of advanced prostate cancer patients," said Karim Fizazi, M.D., Ph.D., Head of the Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, France. "Denosumab showed superior efficacy in preventing skeletal complications, and was generally well tolerated.  These results in conjunction with the convenient subcutaneous dosing and without the need for renal monitoring, show that denosumab has the potential to be a meaningful advance over current treatments."

Overall rates of adverse events (AEs) and serious adverse events, including infections, were generally similar between the two arms. Osteonecrosis of the jaw (ONJ) was infrequent (22 patients receiving denosumab (2.3 percent) as compared with 12 patients receiving Zometa (1.3 percent)); the incidence of ONJ was not significantly different between treatment arms. As with previous studies in advanced cancer patients, hypocalcemia was more frequent in the denosumab arm.

This study is the final of three pivotal trials involving over 5,700 advanced cancer patients that explored the potential of denosumab to treat bone metastases. These three studies form the basis of the clinical evidence package for denosumab in advanced cancer, and were submitted to regulatory authorities in the United States (U.S.) and in the European Union (EU).