Amgen has announced that the European Commission (EC) has approved a new indication for 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.
This news follows the recent announcement that the committee for medicinal products for human use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion in the marketing authorisation of Prolia for the treatment of the same condition in the same patient population.
“Long-term glucocorticoid therapy is associated with a rapid and early decline in bone mineral density and increase in fracture risk,” says Willem F Lems (VU University Medical Centre, Amsterdam, The Netherlands). “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 randomised, 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 at 12 months, assessing non-inferiority) and all secondary endpoints (the percent changes from baseline in lumbar spine and total hip bone mass density at 12 and 24 months, assessing superiority).
In the glucocorticoid-continuing subpopulation, Prolia demonstrated a greater increase in lumbar spine bone mineral density compared to risedronate at one year (Prolia 3.6%, risedronate 2%; p<0.001) and two years (Prolia 4.5%, risedronate 2.2%; p<0.001). In the glucocorticoid-initiating subpopulation, Prolia demonstrated a greater increase in lumbar spine bone mass density compared to risedronate at one year (Prolia 3.1%, risedronate 0.8%; p<0.001) and two years (Prolia 4.6%, risedronate 1.5%; p<0.001).
In addition, compared with risedronate, Prolia demonstrated significantly greater mean percent increases in bone mass density 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% or greater in either treatment group.
The US Food and Drug Administration (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.