Forearm Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis: Results from the Abaloparatide-SC Phase 3 Trial (ACTIVE)

Presentation Number: LB SUN 46
Date of Presentation: April 2nd, 2017

Nelson B. Watts*1, Lorraine A Fitzpatrick2, Gregory C Williams3, Gary Hattersley3, Yamei Wang4, Paul D Miller5 and Felicia Cosman6
1Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, 2Radius Health, Inc, Wayne, PA, 3Radius Health, Inc, Waltham, MA, 4Radius Health, Inc, Parsippany, NJ, 5Colorado Center for Bone Research, Lakewood, CO, 6Helen Hayes Hospital, West Haverstraw, NY; and Columbia University College of Physicians and Surgeons, New York, NY

Abstract

Abaloparatide-SC (ABL-SC) is an investigational drug that binds to the parathyroid hormone 1 receptor resulting in an osteoanabolic effect. ABL-SC is under development for the treatment of postmenopausal osteoporosis. In the 18-month Phase 3 ACTIVE study, ABL-SC increased BMD and decreased the risk of vertebral and nonvertebral fractures vs placebo, and decreased the risk of major osteoporotic fractures vs teriparatide. The objective of these analyses of ACTIVE was to determine the efficacy of ABL-SC on an anatomical site with a high proportion of cortical bone (the 1/3 radius) and a site perhaps more relevant to wrist fractures (the ultradistal radius), and to assess the effect of teriparatide and ABL-SC treatment on the risk of wrist fractures.

Changes in BMD at the 1/3 and ultradistal radius at 18 months vs baseline were measured by DXA in a large subset of 982 postmenopausal women enrolled in ACTIVE (n=334, 321, and 327 in the placebo, ABL-SC, and teriparatide groups, respectively). BMD measurements were centrally analyzed and corrected for variation in DXA instruments, and instrument manufacturer was included as a fixed effect in statistical models. Wrist fractures were ascertained in the total cohort of 2463 women randomized to placebo or ABL-SC 80 µg, or open-label teriparatide 20 µg daily, for 18 months.

At 18 months, the mean percent change in BMD at the ultradistal radius increased from baseline in the ABL-SC group (+1.0%) compared with decreases in the placebo group (-1.2%, p<0.0001) and the teriparatide group (-0.5%, p<0.001). The mean percent changes in BMD from baseline at the 1/3 radius were -0.6%, -1.0%, and -2.3% in the placebo, ABL-SC, and teriparatide groups, respectively. Changes at the 1/3 radius were not significantly different between the ABL-SC and the placebo groups (p=0.19); however, the decrease was greater in the teriparatide group compared with ABL-SC (p<0.001) and compared with placebo (p<0.0001). Seven women with wrist fractures in the ABL-SC group (Kaplan-Meier estimate 1.0%), 15 in the placebo group (2.2%), and 17 in the teriparatide group (2.3%) were reported. There was a lower, but not statistically significant, risk of wrist fracture in the ABL-SC group compared with the teriparatide group (HR=0.43, 95% CI [0.18, 1.03], p=0.052).

In conclusion, BMD decreases at the predominantly cortical 1/3 radius were similar for the ABL-SC and placebo treatment groups but were greater for the teriparatide group. Additionally, BMD increased significantly at the more trabecular ultradistal radius in the ABL-SC group compared with both the placebo and the teriparatide groups. These data are consistent with the numerically lower risk of wrist fractures in women treated with ABL-SC compared with teriparatide. These data are also consistent with the reduction in nonvertebral fractures, sites rich in cortical bone, with ABL-SC compared with placebo treatment observed during ACTIVE.

 

Disclosure: NBW: Founder, Osteodynamics, Speaker, Amgen, Speaker, Shire, Consultant, Abbvie, Consultant, Amgen, Consultant, Jansen Pharmaceuticals, Consultant, Merck & Co., Consultant, Radius Health, Inc., Consultant, Sanofi, Researcher, Shire. LAF: Employee, Radius Health, Inc, Employee, Radius Health, Inc.. GCW: Employee, Radius Health, Inc, Employee, Radius Health, Inc.. GH: 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, Ultragenyx, 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. FC: Consultant, Lilly USA, LLC, Speaker, Lilly USA, LLC, Researcher, Lilly USA, LLC, Consultant, Amgen, Speaker, Amgen, Researcher, Amgen, Member of advisory committees or review panels, Radius Health, Inc, Member of advisory committees or review panels, Merck & Co., Consultant, Tarsa.