"One of the main effects of untreated postmenopausal osteoporosis is increased risk of fractures, which can have significant impact on a patient's life," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We are pleased to present these new Prolia analyses at this year's meeting, which add to the growing body of evidence supporting proven treatments for osteoporosis."
Postmenopausal osteoporosis (PMO) affects many women after menopause as their ability to form new bone cannot counter balance the rate at which bone is being removed. This bone loss leads to weakened bones over time, increasing the potential for a break.1,2 Such a break, or fracture, may be a life-changing event.3,4 About half of all women over age 50 will have an osteoporosis-related fracture in their remaining lifetime, and once that happens, the chances of another are much higher.5 In order to determine the risk for fracture, T-scores are measured to compare a patient's bone density to that of a healthy, young person of the same sex. A T-score of -2.5 or lower is defined as osteoporosis. The lower the score, the greater the fracture risk can be.6
Selected Prolia Abstracts of Interest
"Percentage of Women Achieving Non-Osteoporotic BMD T-Scores at the Spine and Hip over 8 Years of Denosumab Treatment"
"Denosumab Restores Cortical Bone Loss at the Distal Radius Associated with Aging and Reduces Wrist Fracture Risk: Analyses from the
"Persistence with Osteoporosis Therapies among Osteoporotic Women at High Risk for Fracture within a Commercially-Insured Population in
About the Open-Label Extension Study of the Pivotal Phase 3 Fracture Trial
The pivotal Phase 3 fracture trial, also known as The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM), was an international, randomized, placebo-controlled trial involving 7,868 women 60 to 90 years of age with a BMD T-score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip who were assigned to denosumab, 60 mg every six months, or placebo for three years. The majority of the original participants continued in the open-label extension study, with those in the placebo group all crossing over to denosumab therapy. The 7-year extension phase of the trial will permit evaluation of denosumab for up to 10 years of treatment.
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 approved in the EU plus
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 nonmetastatic prostate cancer.
Prolia is administered as a single subcutaneous injection of 60 mg once every six months. For further information on Prolia, including prescribing information and medication guide, please visit: www.prolia.com.
Important U.S. Safety Information
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. Patients receiving Prolia should not receive XGEVA® (denosumab), as both Prolia and XGEVA contain the same active ingredient, denosumab.
Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia. 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. All patients should be adequately supplemented with calcium and vitamin D.
Osteonecrosis of the jaw (ONJ) and atypical femoral fractures have been reported in patients with Prolia. In the pivotal Phase 3 study of women with postmenopausal osteoporosis (n=7,808), serious infections leading to hospitalizations were reported more frequently in the Prolia-treated patient group. Serious skin infections, as well as infections of the abdomen, urinary tract and ear, were more frequent in patients treated with Prolia. Patients should be advised to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis. Epidermal and dermal adverse events such as dermatitis, rashes and eczema have been reported. Discontinuation of Prolia should be considered if severe symptoms develop.
Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported. In clinical trials in women with postmenopausal osteoporosis, Prolia resulted in significant suppression of bone remodeling. The significance of these findings is unknown. The long-term consequences of the degree of suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as ONJ, atypical fractures and delayed fracture healing. The most common adverse reactions (>5 percent and more common than placebo) in patients with postmenopausal osteoporosis were back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia and cystitis. The most common adverse reactions in men with osteoporosis were back pain, arthralgia and nasopharyngitis. Pancreatitis has also been reported with Prolia in patients with osteoporosis. The most common (per patient incidence >10 percent) adverse reactions reported with Prolia in patients with bone loss receiving androgen deprivation therapy for prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.
The extent to which Prolia is present in seminal fluid is unknown. For men treated with Prolia, there is a potential for fetal exposure if the sexual partner is pregnant. While the risk is likely to be low, patients should be advised of this potential risk.
Important EU Safety Information
The most common (>1 percent) adverse reactions in clinical trials with Prolia in patients with osteoporosis and breast or prostate cancer patients receiving hormone ablation were urinary tract infection, upper respiratory tract infection, sciatica, cataracts, constipation, abdominal discomfort, rash, eczema, pain in extremity and musculoskeletal pain. Skin infections (predominantly cellulitis) leading to hospitalization were reported more frequently in the Prolia group compared with placebo (0.4 percent vs. 0.1 percent) in postmenopausal osteoporosis studies. In breast and prostate cancer studies, serious adverse reactions of skin infection were similar in the Prolia and placebo groups (0.6 percent vs. 0.6 percent). In a Phase 3 placebo-controlled clinical trial in patients with prostate cancer receiving androgen deprivation therapy (ADT), an imbalance in cataract adverse events was observed with Prolia compared with placebo (4.7 percent vs. 1.2 percent). No imbalance in cataract adverse events was observed in postmenopausal women with osteoporosis or in women undergoing aromatase inhibitor therapy for nonmetastatic breast cancer.
Prolia may rarely lead to hypocalcemia. Prolia is contraindicated in patients with hypocalcaemia, and pre-existing hypocalcemia must be corrected by adequate intake of calcium and vitamin D before initiating therapy. Patients with severe renal impairment or receiving dialysis are at greater risk of developing hypocalcemia. In the post-marketing setting, rare cases of severe symptomatic hypocalcemia have been predominantly reported in patients at increased risk of hypocalcaemia, with most cases occurring in the first weeks of initiating therapy. Osteonecrosis of the jaw (ONJ) has been reported rarely in clinical studies in patients receiving denosumab at a dose of 60 mg every 6 months for osteoporosis. In the osteoporosis clinical trial program, atypical femoral fractures were reported rarely in patients treated with Prolia. In the post-marketing setting, rare events of drug-related hypersensitivity, including anaphylactic reaction, have been reported in patients receiving Prolia. Hypersensitivity to the active substance or any of the excipients is a contraindication for Prolia.
Prolia is not recommended for use in pregnant women.
Denosumab Commercialization Collaboration
Amgen and Daiichi Sankyo Company, Limited have a collaboration and license agreement for the development and commercialization of denosumab in Japan.
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