Amgen announces results of Phase 3 trial in the treatment of bone metastases

Amgen (Nasdaq: AMGN) today announced detailed results from a Phase 3 trial evaluating denosumab administered subcutaneously versus Zometa(R) (zoledronic acid) administered as an intravenous infusion in the treatment of bone metastases in 1,776 advanced cancer patients with solid tumors (not including breast and prostate cancer) or multiple myeloma. These results were presented today at the 2009 ECCO 15 - ESMO 34 European Multidisciplinary Congress in Berlin, Germany (Abstract Number: 20LBA).

For the primary endpoint of this study, the median time to first on-study skeletal related event (SRE) (fracture, radiation to bone, surgery to bone, or spinal cord compression) was 20.6 months for those patients receiving denosumab and 16.3 months for those patients receiving Zometa (hazard ratio 0.84, 95 percent CI: 0.71-0.98), which is statistically significant for non-inferiority>

"It is encouraging to see denosumab's efficacy in this broad cancer population. There is no need for renal monitoring or dose adjustments due to renal impairment," said David Henry, M.D., clinical professor of Medicine, Pennsylvania Hospital, Philadelphia, PA, United States of America. "Furthermore, the positive results of this study, combined with the convenience of a monthly subcutaneous injection and without the flu-like symptoms associated with Zometa administration, make this an exciting potential treatment option for advanced cancer patients."

Bone metastases, the spread of tumors to the bone, are a serious concern for many advanced cancer patients. When cancer spreads to the bone, the growing cancer cells weaken and destroy the bone around the tumor. This damage can result in a number of serious bone complications, collectively called skeletal related events.

Denosumab also delayed the median time to first on-study SRE or hypercalcemia of malignancy (HCM) compared to Zometa (hazard ratio 0.83, 95 percent CI: 0.71, 0.97;>

Bone destruction is a major cause of pain in approximately 70 percent of patients with metastatic disease. In an exploratory analysis, patients on the denosumab arm reported worsening of pain later than those on the Zometa arm (57 days versus 36 days, respectively).

Adverse events rates (96 percent denosumab, 96 percent Zometa) and serious adverse events (63 percent denosumab, 66 percent Zometa) were similar between groups and were consistent with what has previously been reported for these two agents. Rates of osteonecrosis of the jaw (ONJ) were balanced and infrequent in both treatment groups (10 patients receiving denosumab as compared with 11 patients receiving Zometa). Infectious adverse events were balanced between the two treatment arms, as was overall survival (hazard ratio 0.95, 95 percent CI: 0.83-1.08;>

Detailed data from a second Phase 3, head-to-head trial evaluating denosumab versus Zometa will be presented Tuesday, Sept. 22, 2009 at 14:15 - 14:30 Central European Summer Time (CEST) in the Presidential Session of ECCO-ESMO (Abstract #2LBA; presentation embargoed until 12:15 CEST Sept. 22, 2009). In this study of 2,049 patients with advanced breast cancer, denosumab met all primary and secondary endpoints and demonstrated superior efficacy compared to Zometa in the treatment of bone metastases.