Amgen (NASDAQ: AMGN) today published a press release that said the U.S. Food and Drug Administration (FDA) will target an action date of April 26, 2012 for the supplemental Biologics License Application (sBLA) (approval) to expand the indication for XGEVA® (denosumab) to treat men with castrate-resistant prostate cancer with the goal of reducing the risk of developing bone metastases. Bone is of the most common places for prostate cancer to spread. If Xgeva is approved in this expanded indication, it would become the first therapy licensed to prevent or delay the spread of prostate cancer metastases to bone.
Xgeva is the first and only RANK Ligand inhibitor approved by the FDA indicated for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. It 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.
It is delivered as an every four week 120 mg subcutaneous injection.
Xgeva was evaluated in over 7,000 patients with cancer. It demonstrated a clinically meaningful improvement compared to the previous standard of care in preventing bone complications. However, it has not demonstrated any survival advantages. Without any survival advantages it is not clear that the FDA will approve the drug.
Patients taking Xgeva have experienced increases in the chances of developing Osteocronosis of the jaw (ONJ), especially when having extensive dental surgery. Xgeva can also cause severe hypocalcemia (low serum calcium levels in the blood).
Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs. Events considered to be SREs include fractures, spinal cord compression, and severe bone pain that may require surgery or radiation. Such events can profoundly disrupt a patient’s life and can cause disability and pain. Despite the failure of Xgeva to improve survival the ope is that the FDA will place value in the delay of SREs.
Besides submitting Xgeva to the FDA in the United States Amgen has also submitted marketing applications in Australia, Mexico, Russia and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi Sankyo Company, Limited and a marketing application was submitted. In addition, Amgen and Glaxo SmithKline (GSK) have a collaboration agreement for the commercialization of XGEVA in a number of countries where Amgen does not currently have a commercial presence. In these countries, marketing applications are filed by GSK.
Joel T Nowak, M.A., M.S.W.