Amgen receives Complete Response Letter from FDA for XGEVA® sBLA for prevention of bone metastases

Amgen (NASDAQ: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter for 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 Complete Response Letter states that FDA cannot approve the application in its present form. The FDA determined that the effect on bone metastases-free survival (BMFS) was of insufficient magnitude to outweigh the risks (including osteonecrosis of the jaw) of XGEVA in the intended population, and requested data from an adequate and well-controlled trial(s) demonstrating a favorable risk-benefit profile for XGEVA that is generalizable to the U.S. population.

“We are reviewing the complete response letter and will work with FDA to determine any next steps,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “The FDA’s action today does not impact the approved indication of XGEVA in the prevention of skeletal-related events in men with bone metastases from prostate cancer, which was acknowledged by the FDA and the advisory committee members who discussed the application.”

About XGEVA

XGEVA is the first-and-only RANK Ligand inhibitor approved by the FDA for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors, including prostate cancer. 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 and disease-free survival in the adjuvant treatment of 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), Australia, Russia, Argentina, Switzerland, and Israel 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.

XGEVA has been approved in Mexico for the prevention of skeletal related events (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in patients with advanced malignancies involving bone. In Japan, Amgen is working with its licensing partner, Daiichi Sankyo Company, Limited, and denosumab is approved as RANMARK® for treatment for bone complications stemming from multiple myeloma and bone metastases from solid tumors.

Amgen has also submitted marketing applications for XGEVA in South Africa, Gulf Cooperation Council countries, Morocco and Egypt. 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.