Amgen to discuss application for new use of XGEVA® (denosumab) at FDA ODAC meeting

Amgen (NASDAQ: AMGN) will discuss the data from 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 (spread of cancer to the bone) at today’s meeting of the U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC).

Amgen will discuss results of the pivotal Phase 3 ‘147 trial, which forms the basis for the proposed new indication. If approved in this expanded indication, XGEVA would become the first therapy licensed to prevent or delay the spread of cancer to bone in men with CRPC. XGEVA is currently approved to prevent skeletal-related events (SREs) in men with advanced prostate cancer that has already spread to the bone.

“The development of bone metastasis is an irreversible, life-changing event for men living with castration-resistant prostate cancer and is associated with significant and progressive morbidity,” said Sean Harper, M.D., senior vice president of Global Development and chief medical officer at Amgen. “XGEVA is the first agent to prolong bone metastasis-free survival and addresses this important unmet medical need.”

Bone metastases weaken the skeleton and can result in incapacitating complications known as SREs, which include fracture, spinal cord compression, radiation and surgery to bone. An estimated 54,000 patients in the U.S. have CRPC with a high risk of developing bone metastases.

‘147 Study Design & Results

Study ‘147 was a randomized, placebo-controlled, multicenter Phase 3 study comparing the treatment effect of XGEVA to placebo in prolonging bone metastasis-free survival, a measure of the time that patients live without progressing to bone metastases. The study enrolled 1,432 men with CRPC who had no bone metastases at baseline, but were at increased risk based on prostate specific antigen (PSA) criteria. The ‘147 study enrolled patients with a PSA greater than or equal to 8 ng/mL or PSA doubling time of 10 or less months.

The primary analysis of the overall ‘147 study population showed that XGEVA significantly reduced the risk for bone metastases or death by 15 percent and increased bone metastasis-free survival, or the time a patient went without developing bone metastasis, by a median of 4.2 months (29.5 versus 25.2 months, respectively; p=0.028). In exploratory analyses of patients with PSA doubling time of 10 months or less (80 percent of the study population), XGEVA prolonged median bone metastasis-free survival time by 6.0 months compared with placebo with a 16 percent reduction in risk. In patients with PSA doubling time of 6 months or less, XGEVA prolonged median bone metastasis-free survival time by 7.2 months compared with placebo with a 23 percent reduction in risk.

Further supporting the clinical relevance of its effects, XGEVA reduced the risk of symptomatic bone metastases by 33 percent and the risk of multiple bone metastases by 24 percent.

Overall survival was similar (HR 1.01; 95 percent CI: 0.85, 1.20; p=0.91) between the XGEVA and placebo groups. The study was not designed to show an overall survival benefit. Patients were taken off treatment once they developed a bone metastasis so they could receive the standard approved treatment for metastatic cancer at the time the study was conducted.

No new safety risks were identified in the study. Adverse events and serious adverse events were relatively similar between the XGEVA and placebo arms. The known risks of hypocalcemia (1.7 percent) and osteonecrosis of the jaw (ONJ) (4.6 percent) were reported with increased frequencies in the XGEVA-treated patients. The yearly rate of ONJ in the XGEVA arm was similar to prior XGEVA trial results. Back pain was the most common adverse event reported in the XGEVA arm of the trial.

About XGEVA

XGEVA is the first-and-only RANK Ligand inhibitor approved by the FDA for the prevention of SREs in patients with bone metastases from solid tumors. 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 tumors.

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 6,000 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 Important Safety Information

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.

The most common adverse reactions in patients receiving XGEVA were fatigue/asthenia, hypophosphatemia and nausea. The most common serious adverse reaction in patients receiving XGEVA was dyspnea. The most common adverse reactions resulting in discontinuation of XGEVA were osteonecrosis and hypocalcemia. Please visit www.amgen.com or www.xgeva.com for full U.S. prescribing information.

XGEVA Regulatory Status

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

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