LAUSR

Abstract Abaloparatide (ABL) is a novel, selective activator of the PTH1 receptor signaling pathway. In the 18-month Phase 3 ACTIVE study in women with postmenopausal osteoporosis (NCT01343004), ABL significantly increased bone mineral density (BMD), and decreased the risk of vertebral (VF), nonvertebral (NVF), and clinical fractures vs placebo (PBO), and major osteoporotic fractures vs PBO and teriparatide (TPTD). The objective of this post hoc analysis was to evaluate the efficacy of ABL in a subset of women representative of commercial insurance enrollees considered to be at high risk for fracture and meeting potential criteria for coverage. In ACTIVE, 2,463 postmenopausal women with osteoporosis were randomized 1:1:1 to double-blind daily ABL 80 µg SC or PBO, or open-label TPTD 20 µg SC for 18 months. This post hoc analysis included women <65 years of age who met the defined utilization management (UM) criteria (baseline T-score at any site of ≤-2.5 and a prevalent VF and/or at least one prior clinical fracture within 5 years of randomization). New VF incidence was evaluated using the modified intent-to-treat (mITT) population, other endpoints were evaluated using the ITT population. Percentage change at 18 months from baseline in BMD at the total hip (TH), femoral neck (FN), and lumbar spine (LS) were calculated. A total of 296 women were identified in the three treatment groups; ABL (n=94), PBO (n=103), and TPTD (n=99) [overall median age: 60 years; range: 49-64 years; mean LS T-score: -2.97]. At baseline, 92 (31%) had a prevalent VF, 234 (79%) reported ≥1 prior NVF in the past 5 years. Percent experiencing any new VF were 1.3%, 7.1%, and 2.3% in ABL, PBO, and TPTD groups, respectively (P=NS). Kaplan-Meier estimated cumulative incidence were 1.3%, 5.7%, and 3.1% for NVF, 2.6%, 8.9%, and 7.6% for clinical fracture, 2.6%, 6.9%, and 3.2% for major osteoporotic fracture, and 1.3%, 4.5%, and 1.0% for wrist fracture in ABL, PBO, and TPTD groups, respectively (all, P=NS). At 18 months, significant increases (P<0.0001) in BMD from baseline were observed for ABL vs PBO at the TH (mean change 3.20% vs -0.12%), FN (2.71% vs -0.67%), and LS (7.81% vs -0.17%), consistent with the overall ACTIVE population results. Results were similar for TPTD vs PBO. BMD improvements with ABL vs PBO were consistent across age subgroups (≤60 vs >60). Among a subgroup of postmenopausal women with osteoporosis representative of commercial insurance enrollees meeting most payers established UM criteria for coverage, ABL resulted in a numerical risk reduction for VF and NVF as well as significant improvements in BMD, compared with PBO. Results from this post hoc analysis suggest ABL may provide a valuable treatment option for a younger population of women who are at risk for fracture whose coverage is through commercial insurance. Funding: Radius Health, Inc.