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Amgen Announces Positive Top-Line Results From Phase 3 Study Of Prolia® (Denosumab) In Patients Receiving Glucocorticoid Therapy
Study Indicates That Prolia Led to Greater Gains in Bone Mineral Density at 12 Months Compared With Risedronate in Patients Receiving Glucocorticoid Therapy

THOUSAND OAKS, Calif., Aug. 29, 2016 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced positive top-line results from the primary analysis conducted in a Phase 3 randomized, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of Prolia® (denosumab) compared with risedronate in patients receiving glucocorticoid treatment. The study met all primary and secondary endpoints at 12 months. The data showed that treatment with Prolia for 12 months, compared to risedronate, led to significantly greater gains in bone mineral density (BMD) at the lumbar spine and total hip, both in patients receiving continuing glucocorticoid therapy and in patients newly initiating glucocorticoid therapy.   

"The impact of glucocorticoid therapy on bone strength is frequently underestimated, and often leads to increased bone loss and ultimately, a fracture," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We are excited that these data support the potential for Prolia use in patients with glucocorticoid-induced osteoporosis, the most common drug-induced form of the disease."

Results from the glucocorticoid-induced osteoporosis (GIOP) study 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 vs. 2.3 percent, respectively) and total hip (2.1 percent vs. 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 vs. 0.8 percent, respectively) and total hip (1.7 percent vs. 0.2 percent, respectively).

Adverse events (AEs) and serious adverse events (SAEs) were similar across treatment groups and consistent with the known safety profile of Prolia. No SAEs were reported with a subject incidence of two percent or greater in either treatment group. 

This is a Phase 3 international, multi-center, randomized, double-blind, double-dummy, active-controlled, parallel-group study in men and women receiving oral glucocorticoid therapy. A total of 795 patients were enrolled in the 24-month study to evaluate the safety and efficacy of treatment with Prolia 60 mg subcutaneously every six months compared with oral risedronate 5 mg daily in two patient subpopulations: 505 patients receiving continuing glucocorticoid therapy (defined as patients receiving greater than or equal to 7.5 mg daily prednisone or its equivalent for three months or longer and planning to continue treatment for a total of at least six months) and 290 patients newly initiating glucocorticoid therapy (defined as patients receiving greater than or equal to 7.5 mg daily prednisone or its equivalent for less than three months and who are planning to continue treatment for a total of at least six months).

Evaluation of the primary endpoint (the percent change from baseline in lumbar spine BMD at 12 months, assessing non-inferiority) and two secondary endpoints assessed at 12 months (the percent change from baseline in lumbar spine and total hip BMD, assessing superiority) was conducted; further analysis of these results is ongoing and will be submitted to a future medical conference and for publication. The study remains double-blinded and ongoing for an additional 12 months.

About Glucocorticoid-induced Osteoporosis

Glucocorticoid-induced osteoporosis (GIOP), the most common form of secondary osteoporosis, is caused by taking glucocorticoid medicines which are commonly used to treat inflammatory diseases.i Within the first three months of glucocorticoid treatment, patient fracture risk increases up to 75 percent, although BMD will continue to decline significantly in the months to follow.ii

About Prolia® (denosumab)

Prolia is the first approved therapy that specifically targets RANK Ligand, an essential regulator of bone-removing cells (osteoclasts). Prolia is approved and marketed in over 80 countries worldwide.

Prolia is approved in the U.S. for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In the U.S., Prolia is also approved for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer in the U.S.

Prolia is approved in the EU for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures. Prolia is also approved in the EU for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures.

Prolia is administered as a single subcutaneous injection of 60 mg once every six months. Please see the Important Safety Information below.

Important Safety Information (U.S.)

Contraindications

Prolia is contraindicated in patients with hypocalcemia. Pre‐existing hypocalcemia must be corrected prior to initiating Prolia. Prolia is contraindicated in women who are pregnant and may cause fetal harm. Prolia is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling and urticaria.

Same Active Ingredient

Prolia contains the same active ingredient (denosumab) found in XGEVA®. Patients receiving Prolia should not receive XGEVA®.

Hypersensitivity

Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Prolia.

Hypocalcemia

Hypocalcemia may worsen with the use of Prolia, especially in patients with severe renal impairment. In patients predisposed to hypocalcemia and disturbances of mineral metabolism, clinical monitoring of calcium and mineral levels is highly recommended within 14 days of Prolia injection. Adequately supplement all patients with calcium and vitamin D.

Osteonecrosis of the Jaw (ONJ)

ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving Prolia. An oral exam should be performed by the prescriber prior to initiation of Prolia. A dental examination with appropriate preventive dentistry is recommended prior to treatment in patients with risk factors for ONJ such as invasive dental procedures, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders. Good oral hygiene practices should be maintained during treatment with Prolia. The risk of ONJ may increase with duration of exposure to Prolia.

For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. Extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of Prolia should be considered based on individual benefit-risk assessment.

Atypical Femoral Fractures

Atypical low-energy, or low trauma fractures of the shaft have been reported in patients receiving Prolia. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with anti-resorptive agents.

During Prolia treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of Prolia therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Serious Infections

In a clinical trial (N= 7808) in women with postmenopausal osteoporosis, serious infections leading to hospitalization were reported more frequently in the Prolia group than in the placebo group. Serious skin infections, as well as infections of the abdomen, urinary tract and ear were more frequent in patients treated with Prolia.

Endocarditis was also reported more frequently in Prolia-treated patients. The incidence of opportunistic infections and the overall incidence of infections were similar between the treatment groups. Advise patients to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis.

Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections. In patients who develop serious infections while on Prolia, prescribers should assess the need for continued Prolia therapy.

Dermatologic Adverse Reactions

In the same clinical trial in women with postmenopausal osteoporosis, epidermal and dermal adverse events such as dermatitis, eczema and rashes occurred at a significantly higher rate with Prolia compared to placebo. Most of these events were not specific to the injection site. Consider discontinuing Prolia if severe symptoms develop.

Musculoskeletal Pain

Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking Prolia. Consider discontinuing use if severe symptoms develop. 

Suppression of Bone Turnover

In clinical trials in women with postmenopausal osteoporosis, Prolia resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance of these findings and the effect of long-term treatment are unknown. Monitor patients for these consequences, including ONJ, atypical fractures, and delayed fracture healing.

Adverse Reactions

The most common adverse reactions (>5% and more common than placebo) in women with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions (> 5% and more common than placebo) in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. Pancreatitis has been reported with Prolia.

In women with postmenopausal osteoporosis, the overall incidence of new malignancies was 4.3% in the placebo group and 4.8% in the Prolia group. In men with osteoporosis, new malignancies were reported in no patients in the placebo group and 4 (3.3%) patients in the Prolia group. A causal relationship to drug exposure has not been established.

The most common (per patient incidence ≥ 10%) adverse reactions reported with Prolia in patients with bone loss receiving ADT for prostate cancer or adjuvant AI therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. Additionally, in Prolia‐treated men with nonmetastatic prostate cancer receiving ADT, a greater incidence of cataracts was observed.

Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.

Prolia® Postmarketing Active Safety Surveillance Program

The surveillance program is available to collect information from prescribers on specific adverse events. Please see https://www.proliasafety.com/ or call 1‐800‐772‐6436 for more information.

For more information, please see the Prolia Important Safety Information, Prescribing Information, and Medication Guide.

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.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

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CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008 (media)
Kristen Neese, 805-313-8267 (media)
Arvind Sood, 805-447-1060 (investors)

i Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open. 2015;1:e000014.
ii Weinstein RS. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. ASBMR 8th Edition. 2013.

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