OR03-1 The Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Osteoarthritis

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 (OP) (NCT01343004), ABL significantly increased bone mineral density (BMD), and decreased the risk of new vertebral (VF), nonvertebral (NVF), and clinical fractures vs placebo (PBO), and major OP fractures vs teriparatide (TPTD) and PBO. The relationship between osteoarthritis (OA) and OP is unclear. However, increased risk of fragility fracture has been associated with OA despite those patients having higher than average BMD. The objective of this post hoc analysis was to evaluate the efficacy and safety of ABL in patients with OA enrolled in ACTIVE. In ACTIVE, 2,463 postmenopausal women with OP were randomized 1:1:1 to double-blind daily ABL 80 µg or PBO, or open-label TPTD 20 µg, SC for 18 months. Patients were identified as those with medical history of ongoing “osteoarthritis”, “spinal osteoarthritis”, “nodal osteoarthritis”, or “intervertebral disc degeneration.” New VF incidence was evaluated using the modified intent-to-treat (mITT) population, other efficacy endpoints were evaluated using the ITT population. The percent mean changes in BMD from baseline to 18 months were calculated for the total hip (TH), femoral neck (FN), and lumbar spine (LS). A total of 888 patients with ongoing OA were identified in three treatment groups; ABL (n=291), PBO (n=303), and TPTD (n=294) [overall median age: 70 years; range: 50-85 years; mean FN T-score: -2.10]. Most common sites of OA were at the spine (n=336, 38%) and knee (n=328, 37%). At baseline, 196 (22%) patients had a prevalent VF, 208 (23%) reported ≥1 prior NVF within the last 5 years, and 369 (42%) had no prior fractures. Percent experiencing any new VF were 0%, 5.1%, and 0.4% in ABL, PBO, and TPTD, respectively (ABL vs PBO, P<0.001). Kaplan-Meier estimated cumulative incidence for other fracture endpoints was similar across treatment groups. At 18 months, significant increases (P<0.0001) in BMD from baseline were observed for ABL vs PBO at the TH (mean change 3.17% vs -0.35%), FN (2.81% vs -0.36%), and LS (8.78% vs 0.86%), consistent with the overall ACTIVE population results. Most common TEAEs were hypercalciuria (11% vs 10.2%), dizziness (10.7% vs 6.6%), increased creatinine clearance (8.9% vs 10.6%), upper respiratory tract infection (8.6% vs 6.9%), and back pain (7.9% vs 11.6%) for ABL vs PBO groups, respectively. Among postmenopausal women with OP enrolled in ACTIVE, in a subpopulation with prevalent OA, ABL resulted in significant reduction in risk of new VF as well as significant improvements in BMD, vs PBO. Results suggest ABL may be useful in the treatment of women with postmenopausal OP and concurrent OA, at high risk for fracture. Funding: Radius Health, Inc.