OR22-1 Effect of Denosumab Treatment in Postmenopausal Women with Osteoporosis: Eight-Year Results from the Freedom Extension, Phase 3 Clinical Trial

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: OR22-Osteoporosis-Clinical Trials
Sunday, June 22, 2014: 11:30 AM-1:00 PM
Presentation Start Time: 11:30 AM
W181 (McCormick Place West Building)
E Michael Lewiecki1, Socrates Papapoulos2, Kurt Lippuner3, Christian Roux4, Celia JF Lin5, David L Kendler6, Maria L Brandi7, Edward Czerwinski8, Edward Franek9, Peter Lakatos10, Salvatore Minisola11, Jean-Yves Reginster12, Soren Jensen13, Nadia Daizadeh5, Andrea Wang5, Mary Gavin5, Rachel B Wagman5 and Henry G Bone14
1New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, 2Leiden University Medical Center, Leiden, Netherlands, 3Bern University Hospital, Bern, Switzerland, 4Paris Descartes University, Paris, France, 5Amgen Inc., Thousand Oaks, CA, 6University of British Columbia, Vancouver, BC, Canada, 7University of Florence, Florence, Italy, 8Krakow Medical Center, Krakow, Poland, 9Central Clinical Hospital MSWiA, Warsaw, Poland, 10Semmelweis University, Budapest, Hungary, 11Sapienza University, Rome, Italy, 12University of Liège, Liège, Belgium, 13CCBR, Ballerup, Denmark, 14Michigan Bone and Mineral Clinic, Detroit, MI
Purpose: The FREEDOM trial open-label extension (1,2) is designed to evaluate the long-term efficacy and safety of denosumab (DMAb) for up to 10 years. Here we present data from the 5th year of the extension, representing up to 8 years of continued DMAb treatment.

Methods: All women in the extension received 60 mg of DMAb every 6 months and daily calcium and vitamin D. In this analysis, women in the long-term group received 3 years of DMAb in FREEDOM and 5 years of DMAb in the extension, totaling 8 years of DMAb treatment; women in the cross-over group received 3 years of placebo in FREEDOM and 5 years of DMAb in the extension, totaling 5 years of DMAb treatment.

Results: Of the women who entered the extension, 66% completed the 5th year. Bone turnover marker data showed that the reductions in serum C-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide were sustained through 8 years in the long-term group and were similarly reduced in the cross-over group. With 8 years of DMAb treatment in the long-term group, mean bone mineral density (BMD) continued to increase from the FREEDOM baseline for cumulative gains of 18.4% at the lumbar spine (LS) and 8.3% at the total hip (TH) (all p < 0.0001). With 5 years of DMAb treatment in the cross-over group, there were mean BMD increases from the extension baseline of 13.1% at the LS and 6.2% at the TH (all p < 0.0001). The incidence of new vertebral and nonvertebral fracture remained low throughout the extension, and hip fracture incidence was 0.2% and 0.1% for the long-term and cross-over groups, respectively, during year 8. The adverse event (AE) and serious AE profiles were consistent with data reported previously in the extension study.

Conclusions: Treatment with DMAb for up to 8 years was associated with persistent reduction of bone turnover, continued increases in BMD, and low fracture incidence. The benefit/risk profile for DMAb remains favorable.

(1) Papapoulos S et al., JBMR. 2012;27(3):694-701.  (2) Bone HG et al., JCEM. 2013;98(11):4483-4492.

Disclosure: EML: Advisory Group Member, Amgen, Advisory Group Member, Agnovos, Advisory Group Member, Merck, Principal Investigator, Merck, Advisory Group Member, Lilly, Principal Investigator, Lilly, Advisory Group Member, Radius Health, Principal Investigator, Amgen. SP: Speaker, Roche, Medical Advisory Board Member, GlaxoSmithKline, Consultant, Axsome, Speaker, Novartis, Medical Advisory Board Member, Merck & Co., Medical Advisory Board Member, Amgen. KL: Medical Advisory Board Member, Amgen, Medical Advisory Board Member, Eli Lilly & Company, Medical Advisory Board Member, MSD, Medical Advisory Board Member, Takeda, Medical Advisory Board Member, UCB, Investigator, Amgen, Investigator, MSD. CR: Board Member, MSD, Board Member, Lilly, Board Member, Amgen, Principal Investigator, MSD, Principal Investigator, Lilly, Principal Investigator, Bongrain, Speaker, UCB. CJL: Employee, Amgen, Employee, Amgen. DLK: Advisory Group Member, Amgen, Investigator, Amgen, Speaker Bureau Member, Amgen, Advisory Group Member, Eli Lilly & Company, Investigator, Eli Lilly & Company, Speaker Bureau Member, Eli Lilly & Company, Advisory Group Member, Pfizer, Investigator, Pfizer, Speaker Bureau Member, GlaxoSmithKline, Investigator, Astellis, Investigator, Novartis, Advisory Group Member, Merck & Co.. MLB: Principal Investigator, Amgen, Principal Investigator, Eli Lilly & Company, Principal Investigator, MSD, Principal Investigator, Novartis, Principal Investigator, Roche, Principal Investigator, Servier, Consultant, Amgen, Consultant, Eli Lilly & Company, Consultant, MSD, Consultant, Novartis, Consultant, Roche, Consultant, Servier. EC: Investigator, Amgen, Investigator, Servier, Investigator, Merck Serono, Speaker, Servier. EF: Speaker Bureau Member, Servier, Speaker Bureau Member, Novartis, Speaker Bureau Member, MSD, Speaker Bureau Member, Amgen, Advisory Group Member, Novartis, Investigator, Amgen, Speaker Bureau Member, Teva. PL: Advisory Group Member, Amgen, Speaker, Servier, Speaker, Roche. SM: Speaker, Abiogen, Speaker, Amgen, Speaker, Bruno Farmaceutici, Speaker, Eli Lilly & Company, Speaker, Merck Sharp & Dohme, Advisory Group Member, Merck Sharp & Dohme, Advisory Group Member, Amgen. JYR: Investigator, Organon Laboratories, Investigator, Danone, Investigator, Theramex, Investigator, Pfizer, Inc., Investigator, Servier, Investigator, GlaxoSmithKline, Investigator, Novartis Pharmaceuticals, Investigator, Lilly USA, LLC, Investigator, Amgen, Investigator, Roche Pharmaceuticals, Investigator, Teva, Investigator, Rottapharm, Investigator, Merck Sharp Dohme, Investigator, Bristol-Myers Squibb, Speaker, Danone, Speaker, Zodiac, Speaker, Ebewee Pharma, Speaker, Novo Nordisk, Speaker, Nycomed, Speaker, Theramex, Speaker, Analis, Speaker, Teva, Speaker, Teijin, Speaker, Merckle, Speaker, GlaxoSmithKline, Speaker, Roche Diagnostics, Speaker, Servier, Speaker, Novartis Pharmaceuticals, Speaker, IBSA-Genevrier, Speaker, Rottapharm, Speaker, Lilly USA, LLC, Speaker, Merck Sharp Dohme, Consultant, Asahi Kasei, Consultant, UCB, Consultant, Theramex, Consultant, IBSA-Genevrier, Consultant, NPS, Consultant, Nycoed-Takeda, Consultant, Merckle, Consultant, Roche Pharmaceuticals, Consultant, GlaxoSmithKline, Consultant, Amgen, Consultant, Wyeth, Consultant, Lilly USA, LLC, Consultant, Negma, Consultant, Novartis Pharmaceuticals, Consultant, Servier, Investigator, Therabel, Investigator, Boehringer, Investigator, Chiltern, Investigator, Galapagos, Speaker, Will Pharma. ND: Employee, Amgen, Employee, Amgen. AW: Employee, Amgen, Employee, Amgen. MG: Employee, Amgen, Employee, Amgen. RBW: Employee, Amgen, Employee, Amgen. HGB: Principal Investigator, Amgen, Consultant, Amgen, Principal Investigator, Merck, Consultant, Merck, Principal Investigator, Novartis, Consultant, Novartis. Nothing to Disclose: SJ

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

Sources of Research Support: Amgen Inc.
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