FDA Approved Drugs » 2010
Medical Areas: Endocrinology | Musculoskeletal | Obstetrics/Gynecology (Women’s Health) | Family Medicine
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved June 2010
Treatment Area: postmenopausal women with osteoporosis at high risk for fracture
Prolia (denosumab) is a fully human monoclonal antibody that specifically binds to and inhibits the receptor activator of NF-kappaB ligand (RANK Ligand), the primary mediator of bone resorption. RANK Ligand is the protein responsible for activating osteoclasts, the cells that break down bone. An increased amount of the protein has been linked as the primary cause of a broad range of bone loss conditions including osteoporosis, treatment-induced bone loss, bone erosions in rheumatoid arthritis (RA), and bone metastases.
Prolia is supplied as a solution for subcutaneous administration. The recommended initial dose is 60 mg administered as a single subcutaneous injection once every 6 months. Prolia should be administered via subcutaneous injection in the upper arm, the upper thigh, or the abdomen.
FDA ApprovalThe FDA approval of Prolia for the treatment of postmenopausal osteoporosis was based on a 3-year, randomized, double-blind, placebo-controlled trial. The trial enrolled 7,808 women aged 60 to 91 years with a baseline BMD T-score between -2.5 and -4.0 at either the lumbar spine or total hip. Women with other diseases or on therapy that affect bone were excluded. The Women were randomized to receive SC injections of either placebo or Prolia 60 mg once every 6 months. All women received at least 1000 mg calcium and 400 IU vitamin D supplementation daily.The primary efficacy endpoint as the incidence of new morphometric (radiologically-diagnosed) vertebral fractures at 3 years.Effect on vertebral fractures:Prolia significantly reduced the incidence of new morphometric vertebral fractures at 1, 2, and 3 years (p < 0.0001). The incidence of new vertebral fractures at year 3 was 7.2% in the placebo-treated women compared to 2.3% for the Prolia-treated women.Effect on hip fracturesThe incidence of hip fracture was 1.2% for placebo-treated women compared to 0.7% for Prolia-treated women at year 3. Effect on nonvertebral fracturesTreatment with Prolia resulted in a significant reduction in the incidence of nonvertebral fractures: 8.0% in the placebo arm versus 6.5% in the Prolia arm. Effect on bone mineral density (BMD)Treatment with Prolia significantly increased BMD at all anatomic sites measured at 3 years. The treatment differences in BMD at 3 years were 8.8% at the lumbar spine, 6.4% at the total hip, and 5.2% at the femoral neck. BMD returned to approximately baseline levels within 12 months after discontinuation of Prolia therapy.
Adverse events associated with the use of Prolia may include, but are not limited to, the following:
Prolia (denosumab) is a fully human monoclonal antibody that binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Prolia prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.
Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, Hadji P, Hofbauer LC, Alvaro-Gracia JM, Wang H, Austin M, Wagman RB, Newmark R, Libanati C, San Martin J, Bone HG Comparison of the Effect of Denosumab and Alendronate on Bone Mineral Density and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2009 Dec 14:1-34
Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, Wang A, Siddhanti S, Fitzpatrick LA; AMG 162 Bone Loss Study Group Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2007 Dec;22(12):1832-41
For additional information regarding Prolia or osteoporosis and menopause related bone loss, please visit the Prolia web page.