New Data Show Greater Bone Mineral Density Gains With Prolia® (Denosumab) Compared With Zoledronic Acid

Results From Study in Women With Postmenopausal Osteoporosis Previously Treated With Oral Bisphosphonates Presented at ASBMR

Oct 11, 2015, 18:36 ET from Amgen

THOUSAND OAKS, Calif., Oct. 11, 2015 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced findings from a randomized, double-blind, double-dummy, multicenter Phase 4 study showing that Prolia® (denosumab) achieved greater gains in bone mineral density (BMD) than the intravenous bisphosphonate zoledronic acid in postmenopausal women with osteoporosis following previous treatment with oral bisphosphonates. The findings were presented today at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting in Seattle.

"Despite the availability of newer therapies like denosumab, bisphosphonates are commonly used first-line to treat osteoporosis," said lead investigator Paul Miller, M.D., medical director of the Colorado Center for Bone Research, Lakewood, Colo. "Our findings showed that denosumab provides significantly greater bone mineral density increases than zoledronic acid." 

The 12-month study (NCT01732770) included 643 women 55 years or older who had postmenopausal osteoporosis (BMD T-score –2.5 or less at the lumbar spine, total hip, or femoral neck) and had been taking oral bisphosphonate therapy for two or more years. The women were randomized 1:1 to receive either subcutaneous denosumab (60 mg) every six months plus intravenous placebo once yearly (denosumab group, 321 participants), or intravenous zoledronic acid (5 mg) once yearly plus subcutaneous placebo every six months (zoledronic acid group, 322 participants). The change from baseline in lumbar spine BMD at 12 months – the primary endpoint – in the denosumab group was significantly greater than that in the zoledronic acid group: 3.2 percent vs. 1.1 percent, respectively (p<0.0001).

The denosumab group also had significantly greater improvements than the zoledronic acid group in secondary and exploratory study endpoints, including BMD changes in the total hip (1.9 percent vs. 0.6 percent [p<0.0001]), femoral neck (1.2 percent vs. -0.1 percent [p<0.0001]), and 1/3 radius (0.6 percent vs. 0 percent [p<0.0184]).

"These findings add to the evidence supporting Prolia as an important therapeutic option for women with postmenopausal osteoporosis, especially those who have failed bisphosphonate treatment," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Our continued research in this innovative antiresorptive reinforces Amgen's commitment to bone biology and understanding the value Prolia brings to treating osteoporosis in postmenopausal women at high risk for fracture."

In the study, no new safety signals were identified. The two study groups had similar incidences of overall adverse events (AEs), serious AEs, AEs leading to discontinuation, and fatal AEs. Three events consistent with the definition of atypical femoral fracture were observed, including two in the denosumab group and one in the zoledronic acid group. There were no cases of osteonecrosis of the jaw (ONJ), hypocalcemia, or delayed fracture healing.

About Osteoporosis
Excessive bone loss can lead to a condition called osteoporosis, which significantly increases a person's risk for fracture. Women specifically can lose up to 20 percent of their bone mass in the five to seven years after menopause,1 and up to half of all women over the age of 50 will have an osteoporosis-related fracture in their lifetime.2 Postmenopausal osteoporosis, the most common form of the disease,3 is a condition that weakens bones over time, making them thinner, more brittle, and more likely to break.1

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 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. 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 in the U.S. 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.

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.)
Prolia is contraindicated in patients with hypocalcemia. Preexisting 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.

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

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 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.

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®

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 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.

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.

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.

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

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 consequences, including ONJ, atypical fractures, and delayed fracture healing.

The most common adverse reactions (>5 percent 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 percent 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 percent in the placebo group and 4.8 percent in the Prolia® groups. In men with osteoporosis, new malignancies were reported in no patients in the placebo group and 4 (3.3 percent) patients in the Prolia® group. A causal relationship to drug exposure has not been established. Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.

The Prolia Postmarketing Active Safety Surveillance Program is available to collect information from prescribers on specific adverse events. Please see https://www.proliasafety.com/ or call 18007726436 for more information.

For more information, please see the Prolia 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 biologics manufacturing 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.

Forward Looking Statements
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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)

References

1 American College of Preventative Medicine. Osteoporosis: A Resource from the American College of Preventative Medicine. 2009. Available https://c.ymcdn.com/sites/www.acpm.org/resource/resmgr/timetools-files/osteoporosisclinicalreferenc.pdf. Accessed on March 5, 2015.
2 National Osteoporosis Foundation. What Women Need to Know. Available http://nof.org/articles/235. Accessed March 5, 2015.
3 American Academy of Orthopaedic Surgeons. Position Statement: Osteoporosis/Bone Health in Adults as a National Public Health Priority. December 2014. Available http://www.aaos.org/about/papers/position/1113.asp. Accessed on March 5, 2015.

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