Phase 3 Data Demonstrate XGEVA(TM) (Denosumab) is First Bone Targeted Therapy to Prevent Spread of Cancer to the Bone in Men

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Amgen announced primary results of a pivotal Phase 3 trial (‘147) demonstrating that XGEVA(TM) (denosumab) significantly increased bone metastasis-free survival for more than four months in men with castrate-resistant metastatic prostate cancer that has not yet spread to bone. Full results of the ‘147 study were presented for the first time today in a late-breaking plenary session at the American Urological Association (AUA) 2011 Annual Meeting in Washington, D.C. With effective therapies now in place for both early (castrate-sensitive) prostate cancer and advanced (castrate-resistant) prostate cancer, there is a gap in the treatment plan for those patients who are castrate-resistant but have not yet developed metastatic disease. Bone is the most common place for prostate cancer to spread; up to 90 percent of men with prostate cancer will experience bone metastases.(i)(ii)(iii)

The data showed that XGEVA significantly improved median bone metastasis-free survival by 4.2 months, a risk reduction of 15 percent, compared with placebo (29.5 versus 25.2 months, respectively; hazard ratio [HR] 0.85; 95 percent CI: 0.73, 0.98; P=0.028). XGEVA also significantly delayed the time to first bone metastases by 3.7 months compared with placebo (HR 0.84; 95 percent CI: 0.71, 0.98; P=0.032; risk reduction of 16 percent). XGEVA also reduced the risk of bone metastases that were symptomatic by 33 percent (HR 0.67; 95 percent CI: 0.49, 0.92; P=0.01). Overall survival was similar between groups (HR 1.01; 95 percent CI: 0.85, 1.20; P=0.91), and the hazard ratio for progression-free survival was 0.89 (95 percent CI: 0.78, 1.02, P=0.093).

“In this landmark Phase 3 study, XGEVA increased bone metastasis-free survival by preventing bone metastases in men with castration-resistant prostate cancer,” said Matthew Smith, M.D., Ph.D., director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center, Boston. “XGEVA is the first and only bone targeted therapy that has demonstrated the ability to significantly reduce the risk of bone metastasis in men with prostate cancer.”

In the ‘147 trial, adverse events and serious adverse events were relatively similar between the XGEVA and placebo arms. Hypocalcemia and osteonecrosis of the jaw (ONJ) were reported with increased frequencies in the XGEVA treated patients. The yearly rate of ONJ in the XGEVA arm was similar to prior XGEVA trial results. Back pain was the most common adverse event reported in the XGEVA arm of the trial.

Study Design

Study ‘147 was a randomized, placebo-controlled, multi-center Phase 3 study comparing the treatment effect of XGEVA to placebo in prolonging bone metastasis-free survival – a measure of the time that patients live without progressing to bone metastases – in 1,432 men with hormone-refractory (castrate-resistant) prostate cancer with rapidly-rising prostate-specific antigen (PSA) levels who had no bone metastases at baseline. The primary endpoint of the trial was time to first occurrence of bone metastases or death from any cause with secondary endpoints including time to first occurrence of bone metastases (excluding death) and overall survival.

About XGEVA

XGEVA is the first and only RANK Ligand inhibitor approved by the U.S. Food and Drug Administration (FDA) indicated for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma. XGEVA is the first novel bone metastases treatment for advanced cancer patients in nearly a decade. Delivered as an every four week 120 mg subcutaneous injection, XGEVA provides a unique option for urologists and oncologists to prevent skeletal-related events in patients with advanced cancer.

XGEVA is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). XGEVA prevents RANK Ligand from activating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction.

XGEVA has been studied in over 7,000 patients with cancer. In clinical trials, XGEVA demonstrated a clinically meaningful improvement compared to the previous standard of care in preventing bone complications. XGEVA is also being investigated for the potential use to delay the onset of bone metastasis in adjuvant breast cancer.

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