The US Food and Drug Administration (FDA) has invited the Amgen to participate in a meeting of the Oncologic Drugs Advisory Committee (ODAC) on February 8, 2012 to discuss the supplemental Biologics License Application (sBLA) for XGEVA (denosumab) to treat men with castration-resistant prostate cancer (CRPC) at high risk of developing bone metastases.

The ODAC will review results from clinical studies in support of this new indication, including the pivotal '147 trial, a randomized, placebo-controlled, multi-centre phase III study that compared XGEVA to placebo in prolonging bone metastasis-free survival in men with non-metastatic CRPC who were at high risk for bone metastases based on prostate specific antigen criteria.

Amgen plans to discuss the proposed sBLA with ODAC, to support the use of XGEVA in the treatment of men with non-metastatic CRPC; a patient population for whom there are no approved treatments to delay or prevent the spread of cancer to bone.

The sBLA was submitted on June 27, 2011, and a Prescription Drug User Fee Act action date has been scheduled for April 26, 2012. If approved, this will be the second indication for XGEVA in the United States (US).

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 tumours. XGEVA was initially approved following a six month priority review by the FDA. 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 SREs in patients with bone metastases from solid tumours.

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.

XGEVA can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor calcium levels and administer calcium, magnesium and vitamin D as necessary. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA. Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

XGEVA has been approved in the US, Canada, the European Union (EU), Switzerland, Australia and Russia for the prevention of SREs in patients with bone metastases from solid tumours. It is not approved to prevent SREs in patients with multiple myeloma.

Amgen has also submitted marketing applications for XGEVA in Mexico, South Africa, Gulf Cooperation Council countries, Morocco, and Egypt. In Japan, Amgen is working with its licensing partner, Daiichi Sankyo Company, Limited and a marketing application was submitted. In addition, Amgen and GlaxoSmithKline (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.

Bone metastases are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 90 per cent of patients with metastatic disease.