FDA Approves Amgen's XGEVA® (Denosumab) For The Treatment Of Hypercalcemia Of Malignancy Refractory To Bisphosphonate Therapy

This Approval Provides a New Treatment Option for a Patient Population With High Unmet Medical Need

THOUSAND OAKS, Calif., Dec. 8, 2014 /PRNewswire/ -- Amgen (AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved a new indication for XGEVA? (denosumab) for the treatment of hypercalcemia of malignancy (HCM) refractory to bisphosphonate therapy. XGEVA was approved and granted Orphan Drug Designation by the FDA, which is reserved for drugs that are intended for the treatment of rare diseases affecting fewer than 200,000 people in the U.S.

HCM is a serious complication in patients with advanced cancer, including those with hematologic malignancies, and indicates poor prognosis.1,2 The condition results from cancer-driven increases in bone resorption, and if untreated, can lead to renal failure, progressive mental impairment, coma and death.1-3

"Our continued study of XGEVA reinforces Amgen's ongoing commitment to address the unmet needs of cancer patients," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This latest FDA approval for XGEVA provides an important new therapeutic option for patients with a rare condition that cannot be resolved with bisphosphonate therapy."

The approval of XGEVA is based on positive results from an open-label, single-arm study, which enrolled patients with advanced cancer and persistent hypercalcemia after recent bisphosphonate treatment. The primary endpoint was the proportion of patients with a response, defined as albumin-corrected serum calcium (CSC) 11.5 mg/dL (2.9 mmol/L; Common Terminology for Adverse Events [CTCAE] grade 1) within 10 days after the first dose of XGEVA. Secondary endpoints included the proportion of patients who experienced a complete response (defined as CSC 10.8 mg/dL [2.7 mmol/L]) by day 10, time to response and response duration (defined as the number of days from the first occurrence of CSC 11.5 mg/dL). The study achieved its primary endpoint with a response rate at day 10 of 63.6 percent in the 33 patients evaluated. The overall complete response rate was 63.6 percent. The estimated median time to response (CSC 11.5 mg/dL) was nine days, and the median duration of response was 104 days.4,5

The most common adverse reactions in patients receiving XGEVA for hypercalcemia of malignancy were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation and diarrhea.5

For patients with HCM, XGEVA is administered as a subcutaneous injection (120 mg) every four weeks with additional doses of 120 mg on days eight and 15 of the first month of therapy.5

XGEVA binds to RANK Ligand (RANKL), a protein essential for the formation, function and survival of osteoclasts, the cells responsible for bone resorption, thereby modulating calcium release from bone. XGEVA prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction and calcium release.5

About Hypercalcemia of Malignancy

Hypercalcemia of malignancy (HCM) is a serious complication in patients with advanced cancer, including those with hematological malignancies.1 In 2012, the estimated prevalence of HCM in cancer patients in the U.S. was 2.7 percent.6 HCM is indicative of poor prognosis and occurs most often in patients with squamous cell cancer (e.g., lung cancer, head and neck cancer), breast cancer, kidney cancer, myeloma and lymphoma.1,2,7 HCM results from cancer-driven increases in bone resorption, and, if untreated, can lead to renal failure, progressive mental impairment, coma and death.1-3

About XGEVA

XGEVA was approved by the FDA for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors in 2010. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma. In clinical trials, XGEVA demonstrated a clinically meaningful improvement compared to the previous standard of care in preventing SREs. In 2013, XGEVA was approved by the FDA as the first-and-only treatment for adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. (Bioon.com)