Treatment With Prolia(R) (denosumab) Associated With Significantly Greater Adherence, Compliance and Persistence Compared to Alendronate

THOUSAND OAKS, California, March 23, 2011 /PRNewswire/ --

- New 2-Year Open-Label Study Shows More Than 90 Percent of Patients Preferred Prolia Injection Every Six Months Over Weekly Oral Alendronate

Amgen (Nasdaq: AMGN) today announced new data that showed postmenopausal women with osteoporosis had significantly greater adherence, compliance, and persistence during Prolia(R) (denosumab) treatment than during alendronate treatment, an oral bisphosphonate commonly used to treat osteoporosis.

Adherence to treatment, which includes both compliance (a measure of how well patients follow directions for taking medication) and persistence (a measure of whether patients continue with treatment), was measured over two years.

Results from the DAPS (Denosumab Adherence Preference and Satisfaction) study presented at the annual European Congress on Osteoporosis and Osteoarthritis (ECCEO11-IOF) in Valencia, Spain, also found that more than 90 percent of patients preferred Prolia as a treatment option over alendronate. In addition, significantly more patients were satisfied with denosumab injection compared with alendronate tablet (mean score of 4.5 vs. 3.2; score scale of 1-5, higher score, higher satisfaction, p<0.0001).

"Despite the availability of several treatment options, many postmenopausal women with osteoporosis are not taking their medication as prescribed and therefore remain at risk for fractures," said Professor Nick Freemantle, University of Birmingham, Birmingham, UK. "Prolia is an important treatment option for patients not only because of its efficacy and safety, but also because, as this study suggests, women may be more likely to stay on treatment compared to weekly oral alendronate."

DAPS Study Results

DAPS was a two-year, multicenter, open-label, crossover study of 250 postmenopausal women with a bone mineral density (BMD) T-score of less than or equal to -2.0 to greater than or equal to -4.0 at the lumbar spine, total hip, or femoral neck and no prior bisphosphonate treatment. Patients were randomized (1:1) to receive either Prolia every six months in year 1 followed by weekly oral alendronate in year 2, or receive alendronate in year 1 followed by Prolia in year 2.

In the study, 92.4 percent of the patients preferred Prolia over alendronate versus 7.6 percent who preferred alendronate (p<0.0001). Additionally, 91.2 percent preferred Prolia as a treatment option versus 8.8 percent for alendronate (p<0.0001), and overall significantly more patients were more satisfied with treatment with Prolia compared to treatment with oral alendronate.

In patients who received Prolia in the second year of the study, treatment with Prolia compared to alendronate was associated with significantly greater:

    
    - adherence (92.5 percent vs. 63.5 percent, p<0.0001),
    - compliance (93.4 percent vs. 67.8 percent, p<0.0001), and
    - persistence (97.2 percent vs. 71.3 percent, p<0.0001) with treatment.

Patients were considered adherent to treatment if they received two Prolia injections within 6 months (plus or minus 4 weeks) apart, or took greater than or equal to 80 percent weekly oral alendronate and at least two alendronate tablets in the last month, and returned for the final study visit within an allotted time.

The incidence and types of adverse events (AEs) and serious adverse events (SAEs) were generally similar between the Prolia and alendronate patient groups. SAEs were reported in 3.5 percent and 3.9 percent of patients receiving Prolia and alendronate, respectively.

Osteoporosis: Impact, Prevalence and the Role of Adherence

Referred to as a "silent epidemic" by the International Osteoporosis Foundation (IOF), osteoporosis is a global problem that is increasing in significance as the population of the world both increases and ages. The World Health Organization has officially declared osteoporosis a public health crisis, and the IOF is urging governments worldwide to make osteoporosis a healthcare priority.

Osteoporosis-associated fractures are a significant cause of mortality and morbidity. In 2000, the number of osteoporotic fractures in Europe was estimated at 3.79 million, of which 890,000 were hip fractures.(1) Since 2001, the incidence of hip fractures in European countries has risen significantly.(2) In the United States (U.S.), the number of fractures due to osteoporosis is expected to rise to more than three million by 2025.(3)

The direct medical cost of osteoporotic fractures in Europe is expected to rise from euro 31.7 billion in 2000 to euro 76.7 billion in 2050.(4) In 2005, osteoporosis-related fractures were responsible for an estimated $19 billion in cost in the U.S., and this cost is expected to rise to approximately $25 billion by 2025.(5)

Postmenopausal women with osteoporosis who have experienced a fracture are at increased risk for another fracture.(6),(7),(8) Poor adherence can increase fracture risk and has been associated with more fracture-related hospitalizations.(9) Yet globally, adherence to osteoporosis treatments remains low.

    
    - An analysis of data combined over multiple U.S. health plans showed
      that approximately 50 percent of patients discontinue oral
      bisphosphonate therapy within the first year.(10)
    - Data from the UK Health Improvement Network and General Practice
      Research Database showed that less than 50 percent of women in the UK
      continue osteoporosis therapy after six months.(11)
    - In Germany, the IMS(R) Disease Analyser database showed that compliance
      with medication helped reduce the risk for fracture, yet only one third
      of women in the database were still on treatment after one year.(12)

About Prolia

Prolia is the first approved therapy that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone).

Prolia is approved in the European Union (EU) 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.

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 available in 12 European countries, the U.S., Canada and Australia. Applications in the rest of the world are pending.

Prolia is administered as a single subcutaneous injection of 60mg once every six months. For further information on Prolia, please visit: http://www.prolia.com.

Important EU Safety Information

The most common adverse reactions with Prolia were urinary tract infection, upper respiratory tract infection, sciatica, cataracts, constipation, rash, pain in extremity. The most serious adverse reactions were those of skin infections, predominantly cellulitis, reported more commonly 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 the Phase 3 placebo-controlled clinical trial in patients with prostate cancer receiving ADT, an imbalance in cataract adverse events was observed with Prolia compared with placebo (4.7 percent vs. 1.2 percent placebo). 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 lead to hypocalcaemia. Hypocalcaemia must be corrected by adequate intake of calcium and vitamin D before 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.

Important U.S. Safety Information

Prolia is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia. Hypocalcemia may worsen, especially in patients with severe renal impairment. All patients should be adequately supplemented with calcium and vitamin D.

In the pivotal study, 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. Endocarditis was reported more frequently in the Prolia-treated patient group. Epidermal and dermal adverse events such as dermatitis, rashes, and eczema have been reported. Discontinuation of Prolia should be considered if severe symptoms develop.

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. ONJ has been reported in patients with Prolia. Patients should be monitored for these adverse outcomes. The most common adverse reactions (> 5 percent and more common than placebo) were back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. Pancreatitis has also been reported with Prolia.

Denosumab Commercialization Collaborations

In July 2009, Amgen and GlaxoSmithKline 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 Prolia's postmenopausal osteoporosis and potential oncology indications in the U.S. and Canada and for all oncology indications in Europe and in other specified markets.

In addition, GlaxoSmithKline 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, 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, bone disease, 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 vital medicines, visit http://www.amgen.com.

Forward-Looking Statements

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(1) "Facts and statistics about osteoporosis and its impact." International Osteoporosis Foundation. Accessed at http://www.iofbonehealth.org/facts-and-statistics.html#factsheet-category-22 on 4 February 2011

(2) "Osteoporosis in the European Union in 2008: Ten years of progress and ongoing challenges." Accessed at http://www.iofbonehealth.org/publications/eu-policy-report-of-2008.html on 4 February 2011

(3) Burge R, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007: 22::465-475

(4) "Facts and statistics about osteoporosis and its impact." International Osteoporosis Foundation. Accessed at http://www.iofbonehealth.org/facts-and-statistics.html on 4 February 2011

(5) "Fast Facts" National Osteoporosis Foundation. Accessed at http://www.nof.org/node/40 on 4 February 2011

(6) Kanis JA et al. A Meta-Analysis of Previous Fracture and Subsequent Fracture Risk. Bone. 2004;35(2):375-82.

(7) Lindsay R et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001 Jan 17;285(3):320-33.

(8) Klotzbuecher CM et al. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. 2000 Apr;15(4):721-39.

(9) Siris ES et al. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc. 2006 Aug;81(8):1013-22.

(10) Weycker D. et al. Compliance with drug therapy for postmenopausal osteoporosis. Osteoporos Int. 2006;17(11):1645-52. Epub 2006 Jul 22.

(11) Li L, Roddam A, Gitlin M, Taylor A, Shepherd S, Jick S. Retrospective Analysis of Persistence to Anti-Osteoporosis Medications in the UK General Practice Research Database (GPRD). Poster P606. Presented at IOF WCO-ECCEO 2010

(12) Hadji P, Claus V, Steinle T, Kostev K, Intorcia M. Non-adherence in women with osteoporosis treated with oral bisphosphonates: German Retrospective cohort Analysis on Non-aDherence (GRAND). Poster P604. Presented at IOF WCO-ECCEO 2010

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