Denosumab Receives Conditional Approval from FDA Expert Panel

Denosumab Receives Conditional Approval from FDA Expert Panel

Denosumab is a new human monoclonal antibody that suppresses osteoclast function and thus inhibits bone resorption. It is being evaluated by the FDA for treatment of osteoporosis in men and women, and although it has not yet been approved, a recent FDA Expert Panel has given conditional approval paving the way for full FDA approval this fall. Two recently published, industry-sponsored studies suggest the drug is effective in 2 different populations. In the first study, more than 1400 men receiving androgen-deprivation therapy for nonmetastatic prostate cancer were randomly assigned to receive denosumab 60 mg SQ every 6 months or placebo for 2 years. The primary endpoint was change in bone mineral density (BMD) at the lumbar spine, with secondary endpoints of change in BMD in the hip as well as fracture incidence. At 24 months, BMD increased in the lumbar spine with denosumab (5.6% increase vs 1% decrease for placebo; P < 0.001). BMD was also increased in the total hip, femoral neck, and distal radius, and the effect was maintained for 36 months. New fracture rate was also decreased with treatment (1.5% vs 3.9% with placebo; P = 0.006). Rates of adverse events were similar in both groups (Smith MR, et al. N Engl J Med 2009;361:745-755).

In the second study, 7868 postmenopausal women with low BMD were randomized to denosumab 60 mg SQ every 6 months or placebo for 36 months. The primary endpoint was new vertebral fractures. Denosumab was associated with a reduction in vertebral fractures (2.3% vs 7.2% placebo; P < 0.001), a reduction in hip fractures (0.7% vs 1.2% placebo; P = 0.04), and a smaller reduction in nonvertebral fractures. There was no increase in risk of cancer, infection, cardiovascular disease, delayed fracture healing, hypocalcemia, or osteonecrosis of the jaw in this study (Cummings SR, et al. N Engl J Med 2009;361:756-765).

These last findings are important because the FDA's Expert Panel expressed concerns about infection and cancer data in giving a recommendation to approve denosumab when the FDA votes on the drug in October. If approved, which seem likely, denosumab will be marketed by Amgen under the trade name Prolia™.