FDA Approves Denosumab for Glucocorticoid-Induced Osteoporosis

Today Amgen announced that Prolia (denosumab) received US Food and Drug Administration (FDA) approval for the treatment of glucocorticoid-induced osteoporosis (GIOP) in men and women at high risk of fracture.

This is the fifth indication for the drug, which is designed to target RANK Ligand, an essential regulator of bone-removing cells (osteoclasts).

"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 FDA approval is based on results from a phase 3 study which reported greater gains in bone mineral density for patients taking denosumab compared to those who received an active comparator (risedronate).

The randomized, double-blind, double-dummy, active-controlled study of 795 patients evaluated the safety and efficacy of denosumab (60mg subcutaneously every 6 months) compared with risedronate (5mg orally once daily). All participants were receiving glucocorticoid treatment ≥7.5mg/day of oral prednisone or equivalent.

Patients were evaluated in groups based on how long they had received glucocorticoid treatment. The glucocorticoid-initiating group had received treatment for <3 months at baseline while the glucocorticoid-continuing group had received treatment for ≥3 months prior to study enrollment.

Study results indicated that in the glucocorticoid-continuing group, denosumab demonstrated a significantly greater increase in lumbar spine bone mineral density (BMD) compared to risedronate at 1 year (3.8% versus 0.8%, respectively) with a treatment difference of 2.9% (p<0.001).

Additionally, in the glucocorticoid-initiating group, denosumab demonstrated a significantly greater increase in lumbar spine BMD compared to risedronate at 1 year (4.4% versus 2.3%, respectively) with a treatment difference of 2.2% (p<0.001).

"This is a serious condition that leads to rapid decreases in bone mineral density and increased risk of fracture. This approval gives patients and physicians a new treatment option," said Sean E. Harper, MD, executive vice president of Research and Development at Amgen.

The safety results were consistent with established safety profile for denosumab. The most commonly reported adverse reactions (>3% and more common than active-control group) were back pain, hypertension, bronchitis, and headache.

Researchers reported serious infection in 15 patients (3.9%) in the active-control group and 17 patients (4.3%) in the denosumab group. Epidermal and dermal adverse events, including dermatitis, eczema, and rashes, were reported in 16 patients (4.2%) in the active-control group and 15 patients (3.8%) in the denosumab group.

For women with postmenopausal osteoporosis, the most common adverse reactions (occurring >5% and more common than placebo) to denosumab were back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions in men with osteoporosis were back pain, arthralgia, and nasopharyngitis.

"As a leader in bone health with more than 20 years of osteoporosis research experience, we are pleased that Prolia will now be available for patients at high risk of fracture who are suffering from bone loss due to long-term glucocorticoid treatment," said Harper.