Data Include Eight Year Analyses of Bone Mineral Density Results for Prolia® (Denosumab) and Further Evidence for Significant Bone-Building With Romosozumab
THOUSAND OAKS, Calif., Sept. 10, 2014 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced that it will present data from multiple Prolia® (denosumab) and romosozumab study analyses at the American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting being held in Houston, Sept. 12-15, 2014. The data that will be presented reinforce Amgen's continued commitment to discovering and developing novel treatments for patients suffering from bone-related diseases.
Prolia data consist of 18 abstracts, including several exploratory analyses evaluating eight years of Prolia therapy from the open-label extension study of the pivotal Phase 3 fracture trial. Analyses report the percentage of women who achieved non-osteoporotic bone mineral density (BMD) T-scores and the long-term effects of Prolia on reducing cortical bone loss. A separate analysis reports compliance and persistence among women at high risk of fracture identified in a commercially-insured database. Data for romosozumab include two exploratory analyses from the Phase 2 trial and open-label extension study in postmenopausal women with low BMD. The first analysis evaluated the effect of treatment with romosozumab over two years, as well as data on a third year where patients received either Prolia or placebo; another examined the effect of romosozumab treatment on vertebral cortical mass, thickness and density. Romosozumab is being co-developed by Amgen and UCB (Euronext: UCB).
"Given that more than 200 million women worldwide have osteoporosis,1 and many of these have experienced a fracture, additional therapies are needed to help manage the continuum of the disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Limited data exists on the risks and benefits of the long-term treatment of osteoporosis, and we're excited to help address this gap with the large body of Prolia data we will present at this year's meeting."
SELECTED ABSTRACTS OF INTEREST
Abstracts are available on the ASBMR website at www.asbmr.org and updated data will be presented at the meeting.
Prolia Abstracts of Interest
- Percentage of Women Achieving Non-Osteoporotic BMD T-scores at the Spine and Hip Over 8 Years of Denosumab Treatment, Abstract FR0391, Friday, Sept. 12, 4:15 – 4:20 p.m. CDT (Grand Ballroom BC)
- Denosumab Restores Cortical Bone Loss at the Distal Radius Associated With Aging and Reduces Wrist Fracture Risk: Analyses From the FREEDOM Extension Cross-over Group, Abstract 1047, Saturday, Sept. 13, 3:15 – 3:30 p.m. CDT (Grand Ballroom BC)
- Persistence with Osteoporosis Therapies among Osteoporotic Women at High Risk for Fracture Within a Commercially-Insured Population in the United States, Abstract 1138, Monday, Sept. 15, 8:45 – 9 a.m. CDT (Discovery Hall-Hall E)
Romosozumab Abstracts of Interest
- Romosozumab and Teriparatide Effects on Vertebral Cortical Mass, Thickness, and Density in Postmenopausal Women With Low Bone Mineral Density (BMD), Abstract 1049, Saturday, Sept. 13, 3:30 – 3:45 p.m. CDT (Grand Ballroom BC)
- Effects of 2 Years of Treatment With Romosozumab Followed by 1 Year of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density, Abstract 1152, Monday, Sept. 15, 11:15 – 11:30 a.m. CDT (Grand Ballroom BC)
Osteoporosis 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.2
About half of all women over age 50 will have an osteoporosis-related fracture in their remaining lifetime.3 Only 24 percent of women who suffer an osteoporotic fracture received treatment during the following year.4
The World Health Organization has officially declared osteoporosis a public health crisis, while the International Osteoporosis Foundation urges governments worldwide to make osteoporosis a healthcare priority.
Romosozumab is an investigational bone-forming agent that is designed to work by inhibiting the protein sclerostin, thereby increasing bone formation and decreasing bone breakdown. Romosozumab is being studied for its potential to reduce the risk of fractures in an extensive global Phase 3 program. This program includes two large fracture trials comparing romosozumab to either placebo or active comparator in more than 10,000 patients with osteoporosis. Romosozumab is being co-developed by Amgen and UCB.
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 Switzerland, Norway, Iceland and Liechtenstein 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 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 hospitalisation 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 hypocalcaemia. Prolia is contraindicated in patients with hypocalcaemia, and pre-existing hypocalcaemia 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 hypocalcaemia. In the post-marketing setting, rare cases of severe symptomatic hypocalcaemia 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.
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 the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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1. Kanis JA (2007) WHO Technical Report, University of Sheffield, UK: 66.
2. National Osteoporosis Foundation. Available at: www.nof.org. Accessed on September 5, 2014.
3. National Osteoporosis Foundation. Bone Health Facts. http://nof.org/articles/7. Accessed September 5, 2014.
4. Andrade SE, et al. Low frequency of treatment of osteoporosis among postmenopausal women following a fracture. Arch Intern Med. 2003;163:2052-2057.