ECTS Abstracts (2015) 1 HT5

Treatment with Abaloparatide Significantly Reduces Wrist Fractures Compared to Teriparatide - Results of the Phase 3 ACTIVE Trial

Paul Miller1, Gary Hattersley2, Michael Lewiecki3, Edith Lau4, Peter Alexandersen5, Tomas Hala6, Sorica Mustatea7, Bettina Storgaard Nedergaard8, Annesofie Krogsaa9, Jan Slesinger10, Cristiano A F Zerbini11, Ivo Valter12, Zydrune Visockiene13, Beata Jendrych14, Alan G Harris2, Gregory C Williams2, Ming-yi Hu2, Dennis Black16 & Luis A Russo15

1Colorado Center for Bone Research, Lakewood, CO, USA; 2Radius Health, Inc., Waltham, MA, USA; 3University of New Mexico, Albuquerque, NM, USA; 4CCBR, Hong Kong, China; 5CCBR, Vejle, Denmark; 6CCBR, Pardubice, Czech Republic; 7CCBR, Budapest, Romania; 8CCBR, Aalborg, Denmark; 9CCBR, Ballerup,, Denmark; 10CCBR, Brno, Czech Republic; 11CCBR, Sao Paulo, Brazil; 12CCBR, Tallinn, Estonia; 13CCBR, Vilnius, Lithuania; 14CCBR, Warsaw, Poland; 15CCBR, Rio de Janiero, Brazil; 16University of San Francisco, San Francisco, CA, USA.

Cortical bone contributes significantly to bone strength. Abaloparatide (ABL) is an osteoanabolic analog of PTHrP being developed for the treatment of postmenopausal osteoporosis (PMO). We have recently reported that ABL reduces spine and non-vertebral fracture risk (Miller et al, ENDO 2015). ACTIVE was a randomized, double-blind, placebo-controlled Phase 3 fracture prevention trial in which PMO women received 18-months of daily SC placebo (PBO), ABL 80 μg, or teriparatide (TPTD) 20 μg. To assess the effects of ABL on anatomical sites with a high proportion of cortical bone we measured 1/3 distal radius (1/3R), ultra-distal radius (UDR) bone mineral density (BMD) and the incidence of wrist-fracture in women in a subset of 982 women in the ACTIVE study. After 18-months, mean (±SD) percentage changes from baseline for UDR BMD were 1.21±5.9%, 1.04±6.14%, and -0.54±6.32% in the PBO, ABL and TPD groups, respectively The differences between ABL and PBO, and ABL and TPTD were statistically significant (p<0.001 and p=0.0013). Mean percentage changes from baseline in 1/3R BMD were -0.62±3.97%, -1.02±4.68%, and -2.27±4.54% in the PBO, ABL, and TPTD groups. 1/3R BMD decreased more in the TPTD group vs ABL (p=0.0006) and PBO (p<0.0001). In the PBO group, 1.2% of women experienced a wrist fracture compared to 0.5% in the ABL group and 1.8% in the TPTD group. Risk of wrist fracture was significantly reduced with ABL vs TPTD (hazard ratio [HR]=0.28; Log-rank p=0.015) but not significantly vs PBO (HR=0.42; NS). These results indicate that BMD decreases at the radius were less with ABL than TPTD, consistent with the lower incidence of wrist fracture in women treated with 18-months of ABL vs TPTD. The observed differential effects of these agents on wrist fracture and BMD may relate to the lower levels of intracortical bone resorption observed in women treated with ABL vs TPTD.

Disclosure: G. Hattersley, AG Harris, GC Williams, and MY Hu are employees of Radius Health, Inc., M Lewiecki is a consultant to Radius, DM Black is a paid consultant to Radius, all other authors were Principle Investigators in the ACTIVE Trial and were compensated for their participation. This study was sponsored by Radius Health, Inc.

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