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FDA Approves Prolia (denosumab) for Glucocorticoid-Induced Osteoporosis

THOUSAND OAKS, Calif., May 21, 2018 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved the use of Prolia (denosumab) for the treatment of glucocorticoid-induced osteoporosis (GIOP) in men and women at high risk of fracture, 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 which showed patients on glucocorticoid therapy who received Prolia had greater gains in bone mineral density (BMD) compared to those who received active comparator (risedronate).

"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 Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "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."

"Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment1," said study lead Kenneth F. Saag, M.D., M.Sc., 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 six 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).2 The study included two patient groups: a glucocorticoid-initiating subpopulation, receiving treatment for less than three months prior to study enrollment and planning to continue treatment for a total of at least six months, and a glucocorticoid-continuing subpopulation, receiving treatment for greater than or equal to three months prior to study enrollment and planning to continue treatment for a total of at least six months. Study results showed that in the glucocorticoid-continuing subpopulation, Prolia demonstrated a significantly greater increase in lumbar spine BMD compared to risedronate at one year (3.8 percent versus 0.8 percent, respectively) with a treatment difference of 2.9 percent (p<0.001). Similarly, in the glucocorticoid-initiating subpopulation, Prolia demonstrated a significantly greater increase in lumbar spine BMD compared to risedronate at one year (4.4 percent versus 2.3 percent, respectively) with a treatment difference of 2.2 percent (p<0.001). 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 percent 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 percent) in the active-control group and 17 patients (4.3 percent) 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 percent) in the active-control group and 15 patients (3.8 percent) in the Prolia group.

About Glucocorticoid-Induced Osteoporosis (GIOP)

GIOP is the most common form of secondary osteoporosis.3 However, the proportion of patients that qualify for GIOP diagnosis and intervention is small and depends on the level of exposure to glucocorticoid medications.4,5 In addition, a significant proportion of the patients treated long-term with glucocorticoid medications are already diagnosed with postmenopausal osteoporosis or treated with osteoporosis medications. Importantly, at similar levels of BMD, postmenopausal women taking glucocorticoids have considerably higher risk of fracture compared with nonusers of glucocorticoids.6 The most frequent chronic inflammatory diseases associated with long-term glucocorticoid use are chronic obstructive pulmonary disorder (COPD), asthma and rheumatoid arthritis.7 In the U.S., more than 10 percent of patients who receive long-term glucocorticoid treatment are diagnosed with a clinical fracture, and in an EU study, 30 to 40 percent had radiographic evidence of vertebral fractures.7,8

About Amgen

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

Amgen Forward-Looking Statements

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1 Weinstein RS. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. ASBMR 8th Edition. 2013.
2 Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, Chapurlat R, Wang A, Pannacciulli N, Lems WF. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Apr 6. pii: S2213-8587(18)30075-5. doi: 10.1016/S2213-8587(18)30075-5..
3 Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open. 2015;1:e000014..
4 Buckley L, et al. Arthritis Care Res (Hoboken). 2017;69:1095–1110..
5 Lekamwasam S, et al. Osteoporos Int. 2012;23:2257-2276..
6 van Staa TP, et al. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 2003;48:3224-3229..
7 Angeli A, Guglielmi G, Dovio A, Capelli G, de Feo D, Giannini S, et al. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone. 2006;39:253-9..
8 Curtis J, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006; 55:420–6.

Source: Amgen

Posted: May 2018

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