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Study Data Support New Use for Bone Drug Denosumab (Prolia)

RANK ligand evaluated in phase 3 trial

Positive results have been reported from a phase 3, randomized, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of denosumab (Prolia, Amgen) compared with that of risedronate (Actonel, Procter & Gamble/Sanofi-Aventis) in patients receiving glucocorticoid treatment. The study met all primary and secondary endpoints at 12 months. The data showed that treatment with denosumab for 12 months led to significantly greater gains in bone mineral density (BMD) at the lumbar spine and total hip, both in patients receiving continuing glucocorticoid therapy and in those newly initiating glucocorticoid therapy, compared with risedronate.

Prolia is the first approved therapy that specifically targets RANK ligand, an essential regulator of bone-removing cells (osteoclasts).

The international, parallel-group study involved 795 men and women receiving oral glucocorticoid therapy. The 24-month study evaluated the safety and efficacy of subcutaneous denosumab (60 mg every six months) compared with that of oral risedronate (5 mg daily) in two subpopulations: 1) 505 patients receiving continuing glucocorticoid therapy (defined as patients receiving at least 7.5 mg daily of prednisone or its equivalent for three months or longer and planning to continue treatment for a total of at least six months); and 2) 290 patients newly initiating glucocorticoid therapy (defined as patients receiving at least 7.5 mg daily of prednisone or its equivalent for less than three months and who are planning to continue treatment for a total of at least six months).

Results from the new study showed that, in patients receiving continuing glucocorticoid therapy, treatment with denosumab led to greater gains in BMD compared with risedronate, both at the lumbar spine (4.4% vs. 2.3%, respectively) and total hip (2.1% vs. 0.6%). Similarly, in patients newly initiating glucocorticoid therapy, denosumab therapy led to greater increases in BMD compared with risedronate, both at the lumbar spine (3.8% vs. 0.8%, respectively) and total hip (1.7% vs. 0.2%).

Evaluations of the primary endpoint (the percent change from baseline in lumbar spine BMD at 12 months, assessing noninferiority) and two secondary endpoints evaluated at 12 months (the percent change from baseline in lumbar spine and total hip BMD, assessing superiority) were conducted; further analysis of these results is ongoing.

The study remains double-blinded and will continue for an additional 12 months.

Denosumab is approved in the United States for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture or multiple risk factors for fracture; or patients who have failed on or are intolerant of other available osteoporosis therapies. In the U.S., denosumab is also approved for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed on or are intolerant of other available osteoporosis therapies. Moreover, denosumab is indicated in the U.S. as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer.

Source: Amgen; August 30, 2016.

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