Xgeva获批适应症有什么？

What are the approved indications? Xgeva was approved in 2010 for use in patients with solid tumor bone metastases to prevent fracture-related events. Xgeva is not suitable for preventing bone-related events in patients with multiple myeloma (MM). In 2013, the FDA approved a new indication for Xgeva for the treatment of adult patients and skeletally mature adolescent patients with giant cell tumor of bone (GCTB) that is unresectable or whose surgical resection may cause serious complications. The drug is also the first and only GCTB treatment drug approved by the FDA.

On June 19, 2017, the U.S. Food and Drug Administration (FDA) has accepted a supplemental biologics license application (sBLA) for Xgeva, which seeks to expand the currently approved indication for the prevention of fractures and other skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma.

Later, the FDA approved the third indication of the monoclonal antibody drug Xgeva for the treatment of hypercalcemia (HCM) caused by malignant tumors refractory to bisphosphonate therapy.

It is a bone resorption inhibitor with a unique mechanism of action. It specifically targets receptor activator of nuclear factor κB ligand (RANK), inhibits osteoclast activation and development, reduces bone resorption, and increases bone density. Denosumab is a drug that targets the RANK ligand. Compared with bisphosphonates that have been clinically used for a long time, Xgeva has the advantage of significantly prolonging the occurrence time of bone damage-related events. Denosumab is the first approved monoclonal antibody that specifically targets RANK ligand. RANK ligand is a transmembrane or soluble protein that is necessary for osteoclasts to maintain their structure, function, and survival. Human RANKL mRNA is mainly found in bones, bone marrow and lymphoid tissues. Its main function in bones is to stimulate the differentiation and activity of osteoclasts and inhibit the apoptosis of osteoclasts.