Amgen Inc. announced that the US Food and Drug Administration (FDA) has approved Xgeva (denosumab), the first and only RANK Ligand inhibitor for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours. Xgeva was approved following a 6 month priority review by the FDA, a designation reserved for drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. Xgeva is not indicated for the prevention of SREs in patients with multiple myeloma.

"Today's approval of Xgeva illustrates what is possible when scientific innovation, commitment and investment come together to advance medicine," said Kevin Sharer, chairman and chief executive officer of Amgen. "A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating. We are pleased to offer this new advance to patients and their healthcare providers."

Bone metastases, the spread of cancer to the bones, are a serious concern for patients with advanced cancer and present a considerable burden to the healthcare system. Weakened bones due to metastases can lead to fractures and compression of the spinal cord and necessitate procedures like major surgery and radiation, designed to prevent or manage bone complications. The primary goal of treatment for bone metastases is to prevent the occurrence of debilitating and costly bone complications, which can disrupt a patient's life and cause disability, pain and hospitalization.

"As many as 3 out of 4 patients with advanced prostate, lung, and breast cancer will experience spread to their bones. Despite the availability of current treatments, a significant proportion of these patients still experience bone complications or are not candidates for existing treatment," said David H. Henry, M.D., clinical professor of medicine, and vice chair, Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Healthcare System. "Based on the compelling science and robust clinical evidence seen with Xgeva, I expect this new option to quickly become a mainstay of cancer care and to play an important role in reducing the incidence of debilitating bone complications in patients with advanced cancer."

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. 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.

The FDA approval of Xgeva is based on the results of three pivotal, phase 3 head-to-head trials that evaluated Xgeva delivered every four weeks as a 120 mg subcutaneous injection versus Zometa (zoledronic acid) delivered every four weeks via a 15-minute intravenous infusion, adjusted for kidney function per the labelled instructions. The clinical programme for Xgeva spanned more than 50 tumour types in over 5,700 patients. In the phase 3 trials, Xgeva demonstrated a clinically meaningful improvement in preventing SREs compared to Zometa. Specifically, in patients with breast or prostate cancer and bone metastases, Xgeva was superior to Zometa in reducing the risk of SREs. In patients with bone metastasis due to other solid tumours or bone lesions due to multiple myeloma, Xgeva was non-inferior (trending towards superiority) to Zometa in reducing the risk of SREs. Superiority was also seen in the integrated analysis of the phase 3 studies.

Overall rates of adverse events and serious adverse events were generally similar between Xgeva and Zometa. Osteonecrosis of the jaw (ONJ) was infrequent, with no statistically significant difference between treatment arms. Hypocalcemia was more frequent in the Xgeva arm. Overall survival and progression-free survival were similar between arms in all three trials.

"As many as 70 per cent of patients with prostate cancer that have metastasized to the bone are not currently receiving therapy to prevent complications from these bone metastases. This may be secondary to urologists lacking comfort or facilities to provide infusion treatment," said Neal D. Shore, M.D., FACS, medical director, Carolina Urologic Research Center. "Xgeva could provide increased treatment care options and accessibility for urologist's who treat advanced prostate cancer; as Xgeva is administered as a subcutaneous injection on a monthly basis. Also, Xgeva does not require dose adjustment for changes in renal function."

Amgen has also submitted marketing applications for Xgeva in the European Union, Australia, Canada and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi-Sankyo Company, Limited and a marketing application was submitted in August.

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient.