Amgen announced positive top-line results from the primary analysis conducted in a phase 3 randomized, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of Prolia (denosumab) compared with risedronate in patients receiving glucocorticoid treatment.
The study met all primary and secondary endpoints at 12 months. The data showed that treatment with Prolia for 12 months, compared to risedronate, 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 patients newly initiating glucocorticoid therapy.
"The impact of glucocorticoid therapy on bone strength is frequently underestimated, and often leads to increased bone loss and ultimately, a fracture," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We are excited that these data support the potential for Prolia use in patients with glucocorticoid-induced osteoporosis, the most common drug-induced form of the disease."
Results from the glucocorticoid-induced osteoporosis (GIOP) study showed that, in patients receiving continuing glucocorticoid therapy, Prolia treatment led to greater gains in BMD, compared with risedronate, both at the lumbar spine (4.4 per cent vs. 2.3 per cent, respectively) and total hip (2.1 per cent vs. 0.6 per cent, respectively). Similarly, in patients newly initiating glucocorticoid therapy, Prolia treatment led to greater increases in BMD, compared with risedronate, both at the lumbar spine (3.8 per cent vs. 0.8 per cent, respectively) and total hip (1.7 per cent vs. 0.2 per cent, respectively).
Adverse events (AEs) and serious adverse events (SAEs) were similar across treatment groups and consistent with the known safety profile of Prolia. No SAEs were reported with a subject incidence of two per cent or greater in either treatment group.
This is a phase 3 international, multi-center, randomized, double-blind, double-dummy, active-controlled, parallel-group study in men and women receiving oral glucocorticoid therapy. A total of 795 patients were enrolled in the 24-month study to evaluate the safety and efficacy of treatment with Prolia 60 mg subcutaneously every six months compared with oral risedronate 5 mg daily in two patient subpopulations: 505 patients receiving continuing glucocorticoid therapy (defined as patients receiving greater than or equal to 7.5 mg daily prednisone or its equivalent for three months or longer and planning to continue treatment for a total of at least six months) and 290 patients newly initiating glucocorticoid therapy (defined as patients receiving greater than or equal to 7.5 mg daily prednisone or its equivalent for less than three months and who are planning to continue treatment for a total of at least six months).
Evaluation of the primary endpoint (the percent change from baseline in lumbar spine BMD at 12 months, assessing non-inferiority) and two secondary endpoints assessed at 12 months (the per cent change from baseline in lumbar spine and total hip BMD, assessing superiority) was conducted; further analysis of these results is ongoing and will be submitted to a future medical conference and for publication. The study remains double-blinded and ongoing for an additional 12 months.
Glucocorticoid-induced osteoporosis (GIOP), the most common form of secondary osteoporosis, is caused by taking glucocorticoid medicines which are commonly used to treat inflammatory diseases. Within the first three months of glucocorticoid treatment, patient fracture risk increases up to 75 per cent, although BMD will continue to decline significantly in the months to follow.
Prolia is the first approved therapy that specifically targets RANK Ligand, an essential regulator of bone-removing cells (osteoclasts). Prolia is approved and marketed in over 80 countries worldwide.
Prolia is approved in the US 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 or are intolerant to other available osteoporosis therapy. In the US, Prolia 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 or are intolerant to other available osteoporosis therapy. Prolia is also indicated 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 non-metastatic prostate cancer in the US.
Prolia is approved in the EU for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures. Prolia is also approved in the EU for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures.
Prolia is administered as a single subcutaneous injection of 60 mg once every six months.