Amgen Inc. (Nasdaq: AMGN) announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has announced a positive opinion for the marketing authorization of Prolia((TM)) (denosumab) for the treatment of osteoporosis in postmenopausal women at increased risk of fractures, and for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. If approved by the European Commission, Amgen would receive marketing authorization for Prolia in all European Union (EU) Member States.
"Nearly two decades ago, Amgen researchers described a fundamental biochemical pathway that controls bone remodeling," said Roger M. Perlmutter, executive vice president of Research and Development at Amgen. "Armed with this information, our scientists identified a targeted therapy that acts via this normal control mechanism to reduce bone loss. Today's announcement by the CHMP offers the hope that this important new therapy will soon be available to European women with post menopausal osteoporosis, and to European men with prostate cancer who, as a result of hormone ablation therapy, have a significantly increased risk of fracture. With its ability to significantly reduce fractures at key skeletal sites throughout the body, a favorable benefit-risk profile, and convenient dosing every six months, Prolia addresses an important unmet medical need."
The CHMP positive opinion is based on data from six Phase 3 trials. Two Phase 3 pivotal studies with fracture endpoints in the osteoporosis and prostate cancer settings demonstrated that Prolia administered as a subcutaneous injection twice yearly (60mg) reduces the incidence of fractures. All six studies showed Prolia's ability to increase bone mineral density at all skeletal sites measured.
Results from the pivotal FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every six Months) study in 7,868 women with postmenopausal osteoporosis showed that women receiving a subcutaneous injection of Prolia twice-yearly experienced a 68 percent reduction in the risk of suffering a new vertebral (spine) fracture compared to those receiving placebo, as well as a 40 percent reduction in the risk of suffering a hip fracture and a 20 percent reduction in the risk of suffering a nonvertebral fracture.(1) Results from the pivotal Hormone AbLation Therapy study in 1,468 men undergoing androgen deprivation therapy (ADT) for non-metastatic prostate cancer showed that patients treated with Prolia experienced a 62 percent reduction in the risk of suffering a new vertebral fracture with Prolia compared to placebo at 36 months, with significant reduction observed as early as month 12.(2) In both pivotal studies, the incidence and types of adverse reactions observed with Prolia were similar to those seen in patients taking a placebo. The most common adverse reactions in both the Prolia and placebo groups were arthralgia, back pain, hypertension, nasopharyngitis, constipation and pain in an extremity. Serious adverse reactions of skin infections, predominantly cellulitis, were reported more commonly in the Prolia group (0.4 percent vs. <0.1 percent) in postmenopausal osteoporosis studies. In breast and prostate cancer studies, serious adverse reactions were similar in the Prolia and placebo groups (0.6 percent vs. 0.6 percent).
Prolia is also under regulatory review in the United States (U.S.), Switzerland, Australia and Canada for the treatment and prevention of postmenopausal osteoporosis and for the treatment of bone loss in patients undergoing hormone ablation therapy for breast or prostate cancer.
About DenosumabDenosumab has a unique mechanism of action. It is the first and only therapy in late stage development that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone). Administered every six months as a subcutaneous injection just under the skin, denosumab helps stop the process that causes bone loss, resulting in greater bone density, stronger bones and reduced risk for fractures at the spine, hip and other non-vertebral sites. Given its potential to inhibit all stages of osteoclast development through a unique and targeted mechanism, denosumab is also being studied in a range of other bone loss conditions including rheumatoid arthritis, and for its potential to delay bone metastases and inhibit and treat bone destruction in patients with advanced cancer. About Osteoporosis
Often referred to as the "silent epidemic," osteoporosis is a global problem that is increasing in significance as the population of the world both increases and ages. It is estimated that 30 percent of postmenopausal women in the EU have osteoporosis.(3) The World Health Organization (WHO) has recently identified osteoporosis as a priority health issue along with other major non-communicable diseases. Osteoporotic fractures impose a significant financial burden to individuals and health services.(4) The total direct medical cost of osteoporosis in Europe has been estimated at more than euro 36 billion annually, and is expected to increase to euro 76.7 billion in 2050 as the population ages.(5) Along with proper diet and weight-bearing exercise, medications can help slow bone loss and reduce the risk of fracture. Yet despite the availability of osteoporosis treatments for more than 10 years, the worldwide lifetime risk of fracture remains high at 30-50 percent for women and 15-30 percent for men(6).It is estimated that fewer than 50 percent of patients adhere to their current therapy for more than one year(7,8,9), which may leave many patients insufficiently protected against bone loss. About Bone Loss Due to Hormone Ablation
Prostate cancer is the most common form of cancer in men in Europe and accounts for over 24 percent of cancer diagnoses.(10) It is common for prostate cancer patients to receive hormone ablation therapies that can lead to a decrease in bone mass and increased risk of fractures. No EMA-approved therapies currently exist for the management of bone loss due to hormone ablation therapy in patients with prostate cancer. About Denosumab Collaborations
In July 2009, Amgen and GlaxoSmithKline (GSK) announced a collaboration agreement to jointly commercialize Prolia for postmenopausal osteoporosis in Europe, Australia, New Zealand and Mexico once the product is approved in these countries. Amgen will commercialize the drug for postmenopausal osteoporosis and oncology in the U.S. and Canada and for all oncology indications in Europe and in other specified markets. In addition, GSK will register and commercialize denosumab for all indications in countries where Amgen does not currently have a commercial presence, including China, Brazil, India and South Korea but excluding Japan. The structure of the collaboration allows Amgen the option of an expanded role in commercialization in both Europe and certain emerging markets in the future. Amgen and Daiichi-Sankyo Company, Limited, have a collaboration and license agreement for the development and commercialization of denosumab in Japan. About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com. 1. Cummings SR, et al. Twice Yearly Denosumab, a Monoclonal Antibody to RANK-ligand, for Prevention of Fractures in Postmenopausal Women with Osteoporosis. N Engl J Med, 2009 Aug. 20; published online at www.nejm.org on Aug. 11, 2009.
2. Smith MR, et al. Denosumab for the Prevention of Bone Loss and Fractures in Men Receiving Androgen Deprivation Therapy in Non-Metastatic Prostate Cancer. N Engl J Med, 2009 Aug. 20; published online at www.nejm.org on Aug. 11, 2009.
3. "Epidemiology." International Osteoporosis Foundation. Accessed at http://www.iofbonehealth.org/health-professionals/about-osteoporosis/epidemiology.html on 10 March 2009
4. Cooper C. The crippling consequences of fractures and their impact on quality of life. Am J Med. 1997;103(2A):12S-17S
5. "Facts and statistics about osteoporosis and its impact." International Osteoporosis Foundation. Accessed at http://www.iofbonehealth.org/facts-and-statistics.html on 10 March 2009
6. International Osteoporosis Foundation (2002). Osteoporosis in the Workplace: The social, economic and human costs of osteoporosis on employees, employers and governments
7. Rossini M et al. Osteoporosis Int. 2006;17:914-921
8. Payer J et al. Biomed Pharmacother 2007;61:191-193
9. McCombs JS et al. Maturitas 2004;48:271-287
10. Ferlay J, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Annals of Oncology, 2007 Feb. 7.