FDA Approves Denosumab for Steroid-Induced Osteoporosis

May 22, 2018

The US Food and Drug Administration (FDA) has approved denosumab (Prolia, Amgen) for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture, defined as 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. 

Denosumab is the first approved therapy for osteoporosis that specifically targets RANK ligand, an essential regulator of bone-removing cells (osteoclasts).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) also recently adopted a positive opinion for the marketing of denosumab in the European Union for the treatment of bone loss associated with long-term systemic glucocorticoid therapy in adults at increased risk of fracture.

This is the fifth indication for denosumab, which is already approved in the United States for the treatment of postmenopausal women with osteoporosis at high risk for fracture; men with osteoporosis at high risk for fracture; women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer; and men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer.

How Long to Give Denosumab for Steroid-Induced Osteoporosis?

Both the US approval and EU positive opinion were based on data from a phase 3 study that showed patients on glucocorticoid therapy who received denosumab had greater gains in bone mineral density (BMD) compared with those who received active comparator, the bisphosphonate risedronate.

The results of this study were recently published in Lancet Diabetes & Endocrinology, as reported by Medscape Medical News.

"Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in BMD within a few months of beginning treatment," said study lead Kenneth F. Saag, MD, professor of medicine at the University of Alabama at Birmingham School of Medicine in an Amgen press release. "With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their BMD."

In an editorial accompanying the publication of the Phase 3 study, Elena Tsourdi, MD, PhD, and Lorenz Hofbauer, MD, PhD, of Technische Universitat Dresden Medical Center, Germany agreed that denosumab "is an important step towards improved treatment options for glucocorticoid-induced osteoporosis."

But they pointed out that BMD "is not the ideal surrogate for trials in patients with glucocorticoid-induced osteoporosis, because it underestimates fracture risk in view of the extraskeletal adverse effects of glucocorticoids on muscle function and falls."

And physicians still don't know how long to continue treatment with denosumab, as investigators in this trial were only able to report results out to 12 months, they noted, adding that discontinuation of denosumab has been shown to lead to a rapid decrease in BMD, at least among postmenopausal women.

And because many patients require long-term, if not life-long, glucocorticoid therapy, they consequently also need concomitant long-term bone-protective therapy, they explained.

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