Comparison of the Geography of Fracture Incidence in Postmenopausal Women with Osteoporosis Treated with Abaloparatide-SC Versus Placebo during the ACTIVE Trial

Presentation Number: OR08-7
Date of Presentation: April 1st, 2017

Michael R McClung*1, Gregory C Williams2, Gary Hattersley2, Lorraine A Fitzpatrick3, Yamei Wang4 and Paul D Miller5
1Oregon Osteoporosis Center, Portland, OR, 2Radius Health, Inc, Waltham, MA, 3Radius Health, Inc, Wayne, PA, 4Radius Health, Inc, Parsippany, NJ, 5Colorado Center for Bone Research, Lakewood, CO

Abstract

Regional heterogeneity has been observed in fracture risk, and geography may impact the efficacy of osteoanabolic agents. Abaloparatide-SC (ABL-SC) is an investigational, novel, selective activator of the PTH 1 receptor signaling pathway. In the global, phase 3 ACTIVE trial of 2463 postmenopausal women with osteoporosis, ABL-SC significantly reduced the risk of vertebral and nonvertebral fractures compared to placebo, and reduced the risk of major osteoporotic fractures compared to teriparatide. Prespecified exploratory analyses of ACTIVE were completed to investigate, across geographic subgroups (North America, South America, Europe, Asia), both the heterogeneity of fracture risk at baseline and the consistency of effect of ABL-SC versus placebo treatment on fracture risk reduction. A post hoc analysis of consistency of effect of ABL-SC versus placebo was also conducted for women of Hispanic/Latino ethnicity versus other women enrolled in ACTIVE.

Country-specific FRAX models were used to calculate 10-year absolute fracture risks at baseline. Relative risk reductions for new vertebral fractures (VF) and hazard ratios for nonvertebral (NVF), clinical (CF), and major osteoporotic (MOF) fractures were calculated for each geographic and ethnic subgroup, and Forest plots were constructed to assess treatment-by-subgroup interactions.

Prevalent VF were observed at baseline in 20.0%, 18.0%, 25.3%, and 18.5% of total (placebo and ABL-SC) patients from North America, South America, Europe, and Asia, and at least one prior NVF was reported in 80.0%, 40.1%, 58.5%, and 32.2%, respectively. Mean FRAX 10-year probabilities were 16.5%, 8.8%, 13.9%, and 17.7% for MOF. The effects of ABL-SC versus placebo on the risks of VF, NVF, CF, and MOF did not differ significantly across geographic regions, as well as for Hispanic/Latino versus other ethnicities, with no significant treatment-by-region interactions (p=0.57, 0.89, 0.83, 0.76, respectively, for geographic subgroups; p=0.35, 0.57, 0.33, and 0.65, respectively, for Hispanic/Latino versus other ethnicities).

In conclusion, despite limitations of subgroup analyses and geographic variability in fracture incidence and risk at baseline, these analyses suggest that the effects of ABL-SC versus placebo on reducing the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures were consistent across prespecified geographic subgroups. Additionally, a post hoc analysis suggests that the effects of ABL-SC versus placebo on fracture risk were also similar for women of Hispanic/Latino ethnicity compared to other women enrolled in ACTIVE.

 

Disclosure: MRM: Consultant, Radius Health, Inc, Consultant, Amgen, Speaker, Amgen. GCW: Employee, Radius Health, Inc, Employee, Radius Health, Inc.. GH: Employee, Radius Health, Inc, Employee, R. LAF: Employee, Radius Health, Inc, Employee, Radius Health, Inc.. YW: Employee, Radius Health, Inc, Employee, Radius Health, Inc.. PDM: Medical Advisory Board Member, Amgen, Medical Advisory Board Member, AgNovos, Medical Advisory Board Member, Lilly USA, LLC, Medical Advisory Board Member, Merck & Co., Medical Advisory Board Member, Radius Health, Inc., Medical Advisory Board Member, Roche Pharmaceuticals, Medical Advisory Board Member, Ultragenix, Researcher, Alexion, Researcher, Amgen, Researcher, Boehringer Ingelheim, Researcher, Immunodiagnostics, Researcher, Eli Lilly & Company, Researcher, Merck & Co., Researcher, Merck Serono, Researcher, National Bone Health Alliance, Researcher, Novartis Pharmaceuticals, Researcher, Radius Health, Inc, Researcher, Roche Diagnostics, Researcher, Regeneron, Researcher, Daiichi Sankyo, Researcher, Ultragenyx.