The European Commission (EC) has approved a new indication for Amgen’s Prolia (denosumab) for the treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture. The EC approval is based on the positive results of a Phase 3 study that evaluated the safety and efficacy of Prolia compared with risedronate in patients receiving glucocorticoid treatment.
“We are pleased that today’s EC approval provides physicians with a new treatment option for bone loss associated with the use of glucocorticoid medications,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “As a leader in bone health with more than 20 years of osteoporosis research experience, we believe that Prolia can address a critical treatment need for patients with glucocorticoid-induced osteoporosis in Europe and globally.”
“Long-term glucocorticoid therapy is associated with a rapid and early decline in bone mineral density and increase in fracture risk,” said Professor Dr. Willem F. Lems, researcher and rheumatologist, VU University Medical Centre, Amsterdam. “This approval provides a new treatment option to effectively counter the detrimental effects of glucocorticoid therapy on bone in patients at increased risk of fracture.”
The EC approval is supported by a Phase 3 randomized, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of Prolia compared with risedronate in patients receiving glucocorticoid treatment. The study included two patient groups: those on sustained glucocorticoid therapy and those newly initiating glucocorticoid therapy. The study met the primary endpoint (percent change from baseline in lumbar spine bone mass density [BMD] at 12 months, assessing non-inferiority) and all secondary endpoints (the percent changes from baseline in lumbar spine and total hip BMD at 12 and 24 months, assessing superiority).
In the glucocorticoid-continuing subpopulation, Prolia demonstrated a greater increase in lumbar spine BMD compared to risedronate at one year (Prolia 3.6 percent, risedronate 2.0 percent; p<0.001) and two years (Prolia 4.5 percent, risedronate 2.2 percent; p<0.001). In the glucocorticoid-initiating subpopulation, Prolia demonstrated a greater increase in lumbar spine BMD compared to risedronate at one year (Prolia 3.1 percent, risedronate 0.8 percent; p<0.001) and two years (Prolia 4.6 percent, risedronate 1.5 percent; p<0.001).
In addition, compared with risedronate, Prolia demonstrated significantly greater mean percent increases in BMD from baseline at one and two years at the total hip, femoral neck and trochanter in both the glucocorticoid-continuing and glucocorticoid-initiating subpopulations. Adverse events and serious adverse events were similar between treatment groups and consistent with the known safety profile of Prolia. No serious adverse events were reported with a subject incidence of two percent or greater in either treatment group.
The U.S. FDA approved the expanded indication of Prolia for the treatment of osteoporosis associated with newly initiating or sustained systemic glucocorticoid therapy in men and women at high risk of fracture on May 18, 2018.
Filed Under: Drug Discovery