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
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
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including its most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those Amgen projects. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for Amgen to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and Amgen expects similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints Amgen has selected. Amgen develops product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as Amgen may have believed at the time of entering into such relationship. Also, Amgen or others could identify safety, side effects or manufacturing problems with its products, including its devices, after they are on the market.
Amgen's results may be affected by its ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing its products and global economic conditions. In addition, sales of Amgen's products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, Amgen's research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Amgen's business may be impacted by government investigations, litigation and product liability claims. In addition, Amgen's business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If Amgen fails to meet the compliance obligations in the corporate integrity agreement between it and the U.S. government, Amgen could become subject to significant sanctions. Further, while Amgen routinely obtains patents for its products and technology, the protection offered by its patents and patent applications may be challenged, invalidated or circumvented by its competitors, or Amgen may fail to prevail in present and future intellectual property litigation. Amgen performs a substantial amount of its commercial manufacturing activities at a few key manufacturing facilities, including in Puerto Rico, and also depends on third parties for a portion of its manufacturing activities, and limits on supply may constrain sales of certain of its current products and product candidate development. In addition, Amgen competes with other companies with respect to many of its marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for Amgen's products are supplied by sole third-party suppliers. Certain of Amgen's distributors, customers and payers have substantial purchasing leverage in their dealings with Amgen. The discovery of significant problems with a product similar to one of Amgen's products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on its business and results of operations. Amgen's efforts to acquire other companies or products and to integrate the operations of companies Amgen has acquired may not be successful. A breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of our systems and our data. Amgen's stock price may be volatile and may be affected by a number of events. Amgen's business performance could affect or limit the ability of the Amgen Board of Directors to declare a dividend or its ability to pay a dividend or repurchase its common stock. Amgen may not be able to access the capital and credit markets on terms that are favorable to it, or at all.
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.
Posted: May 2018
- FDA Approves New Indication For Prolia (Denosumab) For The Treatment Of Bone Loss In Men With Osteoporosis At High Risk For Fracture - September 21, 2012
- FDA Approves New Indications for Prolia (denosumab) for the Treatment of Bone Loss in Patients With Prostate or Breast Cancer Undergoing Hormone Ablation Therapy - September 19, 2011
- FDA Approves Amgen's Prolia (Denosumab) for Treatment of Postmenopausal Women With Osteoporosis at High Risk for Fracture - June 1, 2010
- Amgen Submits Denosumab Biologics License Application to FDA for the Reduction of Skeletal Related Events in Cancer Patients - May 17, 2010
- Amgen Provides Update on Status of Prolia (denosumab) Biologics License Application (BLA) Submitted to the U.S. Food and Drug Administration (FDA) - October 21, 2009
- Amgen Issues Statement on Outcomes of Advisory Committee for Reproductive Health Drugs (ACRHD) Meeting - August 14, 2009
- FDA Accepts Amgen's Submission and Files Biologics License Application for Denosumab - February 18, 2009
- Amgen Submits Biologics License Application for FDA Approval of Denosumab in Women With Postmenopausal Osteoporosis and in Patients Undergoing Hormone Ablation for Either Prostate or Breast Cancer - December 22, 2008
More News Resources
- FDA Medwatch Drug Alerts
- Daily MedNews
- News for Health Professionals
- New Drug Approvals
- New Drug Applications
- Drug Shortages
- Clinical Trial Results
- Generic Drug Approvals
- Monthly Update Archive