Amgen Seeks to Expand Xgeva's FDA Approval

A pivotal phase III study ('147) found that men with castrate-resistant prostate cancer (CRPC) experienced prolonged bone metastasis—free survival with denosumab (Xgeva) versus placebo. Based on the results, Amgen has submitted an application to the FDA to expand Xgeva’s CRPC indication to include lowering the risk of bone metastases development.

Xgeva is now FDA-approved to prevent skeletal-related events (SREs) in CRPC patients whose solid tumors have metastasized to the bone. According to Amgen, if the FDA expands the indication, Xgeva would become the first approved treatment to prevent or delay bone metastases.

The '147 trial randomized 1432 men with CRPC to either Xgeva or placebo. Bone metastasis—free survival in the Xgeva arm versus the placebo cohort was 29.5 months versus 25.2 months, respectively (hazard ratio, 0.85; 95% confidence interval, 0.73-0.98; P = .028).

The incidence and severity of adverse events was similar between the Xgeva and placebo arms.

“Xgeva has the potential to become a significant advance for patients with castrate-resistant prostate cancer who currently have no treatment options to help prevent the spread of cancer to their bones,” said Roger M. Perlmutter, MD, PhD, executive vice president of Research and Development at Amgen.

Denosumab targets the receptor activator of nuclear factor kappa-B ligand (RANKL) protein, a primary signal to promote bone removal. In many bone-loss conditions, this protein is responsible for overcoming the body’s natural defenses against bone loss.