Amgen (Nasdaq: AMGN) announced top-line results from a Phase 3 trial evaluating XGEVA(TM) (denosumab) versus placebo in 1,432 men with castrate-resistant prostate cancer. The trial, known as the ‘147 study, demonstrated that XGEVA significantly improved median bone metastasis-free survival by 4.2 months (HR=0.85, 95 percent CI 0.73-0.98, p=0.03) compared to placebo (primary endpoint), and significantly improved time to first occurrence of bone metastases (secondary endpoint). Overall survival was similar between the XGEVA and placebo groups (secondary endpoint).
Overall rates of adverse events and serious adverse events were generally similar between XGEVA and placebo, with hypocalcemia and osteonecrosis of the jaw (ONJ) observed at increased frequencies in the XGEVA arm. The yearly rate of ONJ in the XGEVA-treated group was similar to what has been observed in prior XGEVA trials.
“Our data demonstrate that XGEVA, which antagonizes the RANK Ligand axis, limits the ability of tumors to colonize bone, an important finding for men at risk for bone metastases and their healthcare providers,” said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. “We look forward to presenting these landmark data at an upcoming medical conference.”
The RANK Ligand pathway, first discovered by Amgen scientists in the mid-1990s, is believed to play a central role in cancer-induced bone destruction, regardless of cancer type. Data suggest that in bone metastasis, the invasion of cancer is facilitated by bone destruction. Hence, increased bone resorption due to increased RANK Ligand expression appears to augment bone metastasis.
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 fromactivating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction and halting release of growth factors, making the environment less conducive to tumor growth.
Source: Amgen