Prolia(R) (denosumab) Open-Label Extension Trial Showed Continued Increase in Bone Mineral Density Over Five Years of Treatment With Similar Safety Profile Observed in Pivotal Trial
The data, which were presented at the annual European CongressOsteoporosis and Osteoarthritis (ECCEO11-IOF) in Valencia, Spain,showed that treatment with Prolia, the first and only approved RANKLigand inhibitor for the treatment of postmenopausal osteoporosis,resulted in robust BMD gains after five continuous years of treatment(13.7 percent for lumbar spine BMD and 7.0 percent for total hipBMD).
The FREEDOM Study and the 5-Year Prolia Data
The pivotal FREEDOM (Fracture REduction Evaluation of Denosumabin Osteoporosis every 6 Months) study established the efficacy andsafety of Prolia based on three years of data from approximately7,800 postmenopausal women. The open-label extension of FREEDOM isevaluating the long-term (up to 10 years) efficacy and safety ofProlia in 4,550 postmenopausal women. Seventy percent of eligiblewomen from the FREEDOM study continued enrollment in the extensionstudy; 2,343 women continued to receive Prolia treatment, and 2,207transitioned from placebo to Prolia.
Continued treatment with Prolia resulted in consistentyear-over-year gains in BMD at the lumbar spine and total hip. Inyears 4 and 5 respectively, women taking Prolia experienced further1.9 percent and 1.7 percent increases in lumbar spine BMD and further0.7 percent and 0.6 percent increases in total hip BMD (all P<0.0001compared with extension baseline).
The incidences of new osteoporotic fractures also remained lowfor women taking Prolia for five years.
The women who transitioned from placebo to Prolia in theextension study showed significant BMD increases during the first twoyears of Prolia treatment: 7.9 percent increase in lumbar spine BMDand 4.1 percent increase in total hip BMD (all P<0.0001 compared withextension baseline).
Rates of adverse events (AEs) were 83.4 percent for women whocontinued on Prolia and 82.8 percent for women transitioned fromplacebo to Prolia. Rates of serious AEs were 18.9 percent and 19.4percent for the two groups respectively. Two subjects in the groupthat transitioned from placebo to Prolia had AEs adjudicated toosteonecrosis of the jaw (ONJ) that healed without furthercomplications. One of these subjects continued Prolia, and onesubject discontinued. No atypical femoral fractures were reported ineither group.
Osteoporosis: Impact and Prevalence
Referred to as a "silent epidemic" by the InternationalOsteoporosis Foundation (IOF), osteoporosis is a global problem thatis increasing in significance as the population of the world bothincreases and ages. The World Health Organization has officiallydeclared osteoporosis a public health crisis, and the IOF is urginggovernments worldwide to make osteoporosis a healthcare priority.
Osteoporosis-associated fractures are a significant cause ofmortality and morbidity. In 2000, the number of osteoporoticfractures in Europe was estimated at 3.79 million, of which 890,000were hip fractures.(1) Since 2001, the incidence of hip fractures inEuropean countries has risen significantly.(2) In the United States(U.S.), the number of fractures due to osteoporosis is expected torise to more than three million by 2025.(3)
The direct medical cost of osteoporotic fractures in Europe isexpected to rise from euro 31.7 billion in 2000 to euro 76.7 billionin 2050.(4) In 2005, osteoporosis-related fractures were responsiblefor an estimated $19 billion in cost in the U.S., and this cost isexpected to rise to approximately $25 billion by 2025.(5)
Prolia is the first approved therapy that specifically targetsRANK Ligand, an essential regulator of osteoclasts (the cells thatbreak down bone).
Prolia is approved in the European Union (EU) for the treatmentof osteoporosis in postmenopausal women at increased risk offractures, and for the treatment of bone loss associated with hormoneablation in men with prostate cancer at increased risk of fractures.
Prolia is approved in the U.S. for the treatment ofpostmenopausal women with osteoporosis at high risk for fracture,defined as a history of osteoporotic fracture, or multiple riskfactors for fracture; or patients who have failed or are intolerantto other available osteoporosis therapy.
Prolia is available in 12 European countries, the U.S., Canadaand Australia. Applications in the rest of the world are pending.
Prolia is administered as a single subcutaneous injection of 60mgonce every six months. For further information on Prolia, pleasevisit: http://www.prolia.com.
Important EU Safety Information
The most common adverse reactions with Prolia were urinary tractinfection, upper respiratory tract infection, sciatica, cataracts,constipation, rash, pain in extremity. The most serious adversereactions were those of skin infections, predominantly cellulitis,reported more commonly in the Prolia group compared with placebo (0.4percent vs. 0.1 percent) in postmenopausal osteoporosis studies. Inbreast and prostate cancer studies, serious adverse reactions of skininfection were similar in the Prolia and placebo groups (0.6 percentvs. 0.6 percent). In the Phase 3 placebo-controlled clinical trial inpatients with prostate cancer receiving ADT, an imbalance in cataractadverse events was observed with Prolia compared with placebo (4.7percent vs. 1.2 percent). No imbalance in cataract adverse events wasobserved in postmenopausal women with osteoporosis or in womenundergoing aromatase inhibitor therapy for nonmetastatic breastcancer.
Prolia may lead to hypocalcaemia. Hypocalcaemia must be correctedby adequate intake of calcium and vitamin D before initiatingtherapy. ONJ has been reported rarely in clinical studies in patientsreceiving denosumab at a dose of 60 mg every 6 months forosteoporosis.
Important U.S. Safety Information
Prolia is contraindicated in patients with hypocalcemia.Pre-existing hypocalcemia must be corrected prior to initiatingProlia. Hypocalcemia may worsen, especially in patients with severerenal impairment. All patients should be adequately supplemented withcalcium and vitamin D.
In the pivotal study, serious infections leading tohospitalizations were reported more frequently in the Prolia-treatedpatient group. Serious skin infections, as well as infections of theabdomen, urinary tract and ear, were more frequent in patientstreated with Prolia. Patients should be advised to seek promptmedical attention if they develop signs or symptoms of severeinfection, including cellulitis. Endocarditis was reported morefrequently in the Prolia-treated patient group. Epidermal and dermaladverse events such as dermatitis, rashes, and eczema have beenreported. Discontinuation of Prolia should be considered if severesymptoms develop.
Prolia resulted in significant suppression of bone remodeling.The significance of these findings is unknown. The long-termconsequences of the degree of suppression of bone remodeling observedwith Prolia may contribute to adverse outcomes such as ONJ, atypicalfractures, and delayed fracture healing. ONJ has been reported inpatients with Prolia. Patients should be monitored for these adverseoutcomes. The most common adverse reactions (> 5 percent and morecommon 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 collaborationagreement to jointly commercialize Prolia for postmenopausalosteoporosis in Europe, Australia, New Zealand and Mexico once theproduct is approved in these countries. Amgen will commercializeProlia's postmenopausal osteoporosis and potential oncologyindications in the U.S. and Canada and for all oncology indicationsin Europe and in other specified markets.
In addition, GlaxoSmithKline will register and commercializedenosumab for all indications in countries where Amgen does notcurrently have a commercial presence, including China, Brazil, Indiaand South Korea but excluding Japan. The structure of thecollaboration allows Amgen the option of an expanded role incommercialization in both Europe and certain emerging markets in thefuture.
Amgen and Daiichi-Sankyo Company Limited have a collaboration andlicense agreement for the development and commercialization ofdenosumab in Japan.
Amgen discovers, develops, manufactures, and delivers innovativehuman therapeutics. A biotechnology pioneer since 1980, Amgen was oneof the first companies to realize the new science's promise bybringing safe, effective medicines from lab to manufacturing plant topatient. Amgen therapeutics have changed the practice of medicine,helping millions of people around the world in the fight againstcancer, kidney disease, rheumatoid arthritis, bone disease, and otherserious illnesses. With a deep and broad pipeline of potential newmedicines, Amgen remains committed to advancing science todramatically improve people's lives. To learn more about ourpioneering science and vital medicines, visit http://www.amgen.com.
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Editor's Note: Prolia(R) (denosumab) currently is notcommercialized in Spain.
CONTACT: Amgen, Thousand Oaks Ashleigh Koss: +1-805-313-6151 (U.S. media) Wendy Woods Williams: +41(41)3692-542 (E.U. media) Arvind Sood: +1-805-447-1060 (investors)
(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 4February 2011
(2) "Osteoporosis in the European Union in 2008: Ten years ofprogress 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 ofosteoporosis-related fractures in the United States, 2005-2025. JBone Miner Res. 2007: 22::465-475
(4) "Facts and statistics about osteoporosis and its impact."International Osteoporosis Foundation. Accessed athttp://www.iofbonehealth.org/facts-and-statistics.html on 4 February2011
(5) "Fast Facts" National Osteoporosis Foundation. Accessed athttp://www.nof.org/node/40 on 4 February 2011
ots Originaltext: AmgenIm Internet recherchierbar: http://www.presseportal.de
Contact:U.S. media - Ashleigh Koss, +1-805-313-6151; E.U. media - WendyWoods Williams: +41(41)3692-542; investors, Arvind Sood: +1-805-447-1060