Fifth indication for Prolia for men and women at high risk for fracture who are receiving systemic glucocorticoids.
The FDA has approved the use of Prolia (denosumab) for the treatment of glucocorticoid-induced osteoporosis (GIOP) in men and women at high risk for fracture, announced Amgen in a press release. High risk of fracture was defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. This approval is based on data from a phase 3 study that showed patients on glucocorticoid therapy who received Prolia had greater gains in bone mineral density (BMD) than those who received an active comparator (risedronate).
“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment,” said study lead Kenneth F. Saag, MD, MSc, professor of medicine at the University of Alabama at Birmingham School of Medicine. “With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their bone mineral density.”
The approval is supported by the 12-month primary analysis of a 24-month phase 3, randomized, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of Prolia 60 mg subcutaneously every 6 months compared with oral risedronate 5 mg once daily in 795 patients receiving glucocorticoid treatment, greater than or equal to 7.5 mg/day oral prednisone (or equivalent).1 The study included two patient groups: a glucocorticoid-initiating subpopulation, receiving treatment for less than 3 months prior to study enrollment and planning to continue treatment for a total of at least 6 months, and a glucocorticoid-continuing subpopulation, receiving treatment for greater than or equal to 3 months prior to study enrollment and planning to continue treatment for a total of at least 6 months.
Study results showed that in the glucocorticoid-continuing subpopulation, Prolia demonstrated a significantly greater increase in lumbar spine BMD compared with risedronate at 1 year (3.8% versus 0.8%, respectively) with a treatment difference of 2.9% (P < .001). Similarly, in the glucocorticoid-initiating subpopulation, Prolia demonstrated a significantly greater increase in lumbar spine BMD compared with risedronate at 1 year (4.4% versus 2.3%, respectively) with a treatment difference of 2.2% (P < .001). Consistent effects on lumbar spine BMD were observed regardless of gender; race; geographic region; menopausal status; and baseline age, lumbar spine BMD T-score, and glucocorticoid dose within each subpopulation.
Safety results were consistent with the known safety profile of Prolia. The most common adverse reactions (greater than 3% and more common than active-control group) were back pain, hypertension, bronchitis, and headache. Atypical femoral fracture was reported in one patient treated with Prolia. Serious infection was reported in 15 patients (3.9%) in the active-control group and 17 patients (4.3%) in the Prolia group. No cases of osteonecrosis of the jaw were reported. Epidermal and dermal adverse events (such as dermatitis, eczema, and rashes) were reported in 16 patients (4.2%) in the active-control group and 15 patients (3.8%) in the Prolia group.
1. Saag KG, Wagman RB, Geusens P, et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. Published online: April 6, 2018. DOI: https://doi.org/10.1016/S2213-8587(18)30075-5.