Denosumab

BeschreibungDenosumab, which was approved in the United States in 2010, is a fully human sequence IgG2 monoclonal antibody that inhibits bone resorption by blocking the activity of receptor activator of nuclear factor-κB ligand (RANKL). RANKL is a TNF family protein that is expressed in both secreted and cell surface forms by a variety of bone marrow cell types andmediates bone resorption through its receptor (RANK),which is found on osteoclasts and osteoclast precursors . Denosumab was discovered using XenomouseTM transgenic mice comprising human immunoglobulin genes. The antibody is approved for treatment of postmenopausal women with osteoporosis at high risk for fracture, and for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Denosumab competes directly with bisphosphonates such as alendronic acid in postmenopausal osteoporosis and with zoledronic acid in both of these indications. It has been shown to have comparable efficacy and safety to bisphosphonates with some tolerability and patient acceptability advantages.

HistoryDenosumab was approved by the FDA approved on June 2010 for the treatment of osteoporosis in postmenopausal women. It further received additional indication approval to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer and women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer in September 2011 and in men with osteoporosis at high risk for fracture in September 2012. An Denosumab biosimilar, Jubbonti, was approved for Health Canada in February 2024. Two denosumab biosimilars—Wyost® (denosumab-bbdz) 11 and Jubbonti® (denosumab-bbdz)—were approved by the FDA in March 2024 for all indications of the reference products Xgeva® and Prolia®; Both biosimilars also received marketing authorization in the EU in May 2024.

VerwendenPrevention and treatment of all forms of osteoporosis or bone loss.