FDA Accepts sBLA for Prolia in Glucocorticoid-Induced Osteoporosis

Amgen announced the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for Prolia (denosumab) for the treatment of patients with glucocorticoid-induced osteoporosis (GIOP). The sBLA, which was submitted on July 28, 2017, is based on a Phase 3 study evaluating Prolia compared with risedronate in patients receiving glucocorticoid treatment. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of May 28, 2018.

Glucocorticoid medications, which are used to treat many inflammatory conditions, can cause significant side effects, including bone loss. GIOP is the most common form of secondary osteoporosis, and it is estimated that one percent of the U.S. population is treated long-term with glucocorticoid medications. Within the first three months of beginning glucocorticoid treatment, fracture risk increases by up to 75 percent, with bone mineral density (BMD) continuing to decline significantly in the months that follow.

"We believe that Prolia can address a critical treatment need for patients with glucocorticoid-induced osteoporosis, which is the most common drug-induced form of the disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We will continue to work closely with the FDA as they review our application and look forward to expanding Prolia's benefits to patients with this serious condition that is often underestimated and untreated."

The sBLA 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.4 The study included two patient groups: those receiving continuing glucocorticoid therapy and those newly initiating glucocorticoid therapy. The study met the primary endpoint (percent change from baseline in lumbar spine BMD at 12 months, assessing non-inferiority) and all secondary endpoints assessed at 12 months (the percent changes from baseline in lumbar spine and total hip BMD, assessing superiority). Study results showed that, in patients receiving continuing glucocorticoid therapy, Prolia treatment led to greater gains in BMD, compared with risedronate, both at the lumbar spine (4.4 percent versus 2.3 percent, respectively) and total hip (2.1 percent versus 0.6 percent, respectively). Similarly, in patients newly initiating glucocorticoid therapy, Prolia treatment led to greater increases in BMD, compared with risedronate, both at the lumbar spine (3.8 percent versus 0.8 percent, respectively) and total hip (1.7 percent versus 0.2 percent, respectively).

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.

GIOP is the most common form of secondary osteoporosis, and it is estimated that one percent of the U.S. population is treated long-term with glucocorticoid medications. While the number of GIOP patients that overlap with osteoporosis patients is not clear, the most frequent chronic inflammatory diseases associated with long-term glucocorticoid use are chronic obstructive pulmonary disorder (COPD), asthma and rheumatoid arthritis. The exact prevalence is not clear due to overlap with the osteoporosis population. More than 10 percent of patients who receive long-term glucocorticoid treatment are diagnosed with a clinical fracture, and 30 to 40 percent have radiographic evidence of vertebral fractures.