Abstract

Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 signaling pathway. In the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fracture compared with placebo and of major osteoporotic fracture compared with teriparatide. To further evaluate the effectiveness of ABL, we calculated the number needed to treat (NNT) to prevent one fracture using ACTIVE data. To estimate the potential effectiveness of ABL in populations at higher fracture risk than in ACTIVE, we calculated NNT for vertebral fracture using reference populations from historical placebo-controlled trials, assuming an 86% relative risk reduction in vertebral fracture with ABL treatment as observed in ACTIVE. NNT was calculated as the reciprocal of the absolute risk reduction in ACTIVE. The projected NNT for ABL in other populations was calculated based on incidence rate (IR) for vertebral fractures in the placebo arms of the FREEDOM (placebo IR 7.2%), FIT-1 (placebo IR 15.0%), and FIT-2 (placebo IR 3.8%) trials. NNT for ABL in ACTIVE was 28 for vertebral, 55 for nonvertebral, 37 for clinical, and 34 for major osteoporotic fracture. NNT for these fracture types for teriparatide in ACTIVE were 30, 92, 59, and 75, respectively. Using placebo IRs from FREEDOM, FIT-1, and FIT-2, projected NNTs for vertebral fracture with ABL were 17, 8, and 31. These data are useful for further evaluating ABL for the treatment of osteoporosis in postmenopausal women.

Highlights

  • Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway

  • During Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), ABL reduced the risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures compared with placebo and reduced the risk of major osteoporotic fractures compared with TPTD [5]

  • To help understand the potential effects of ABL in populations that may have greater risk of new vertebral fracture than the 4.2% placebo incidence rate (IR) observed in ACTIVE, we explored the potential effectiveness of ABL in historical trial populations, including those with higher placebo IRs than that in ACTIVE

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Summary

Introduction

Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway. ABL binds selectively to the RG versus ­R0 conformation of PTHR1 [1], consistent with a net anabolic effect in contrast with PTH [2]. In the 18-month phase 3 Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE, NCT01343004), treatment with subcutaneously administered ABL for 18 months significantly increased BMD and decreased the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures compared with placebo. ACTIVE included an open-label teriparatide (TPTD) arm, and ABL significantly increased BMD at nonvertebral sites and significantly decreased the risk of major osteoporotic fractures compared with TPTD [5]. To further elucidate the effectiveness of ABL, we evaluated the number needed to treat (NNT) to prevent one fracture (vertebral, nonvertebral, clinical, and major osteoporotic) using data from ACTIVE.

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