Abaloparatide, an investigational parathyroid hormone-related protein (PTHrP) analog, reduced morphometric vertebral fractures, nonvertebral fractures, and major osteoporotic fractures when compared with placebo in postmenopausal women with osteoporosis. These results, derived from the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, ClinicalTrials.gov Identifier NCT01343004), a multicenter, randomized, double-blind, and placebo-controlled trial, were presented at the 2016 annual meeting of the Endocrine Society.
The primary outcome measure in the ACTIVE trial was the number of abaloparatide-treated patients who developed new vertebral fractures at 18 months compared with placebo. Secondary outcome measures included the efficacy of abaloparatide in increasing bone mineral density (BMD) in the lumbar spine, total hip, and femoral neck at 18 months when compared to teriparatide, and the efficacy of abaloparatide on incidence of nonvertebral fractures when compared with placebo.
The investigators found that study participants randomly assigned to receive abaloparatide had significant percentage increases in BMD from baseline in 3 areas when compared with those receiving placebo at 18 months (lumbar spine increased by 9.2%, total hip increased by 3.4%, and femoral neck increased by 2.9%; all P<.0001 vs placebo)
In participants treated with abaloparatide, morphometric vertebral fractures were reduced by 86% (P<.0001), nonvertebral fractures were reduced by 43% (P=.0489), and major osteoporotic fractures were reduced by 70% (P=.0004) when compared with placebo.
Major osteoporotic fractures were reduced by 55% in the abaloparatide treated group as compared with the teriparatide treated group (P=.0309).
After subgroup analysis, the authors found that the risk of new vertebral or nonvertebral fractures decreased uniformly among the study participants taking abaloparatide. This noted decrease appeared to be independent of baseline risk factors.
“Results of forest plots show consistent fracture reduction in the abaloparatide arm for new morphometric vertebral or nonvertebral fractures without any interactions caused by baseline risk factors. Furthermore, there were no interactions between any of the baseline risk factors and magnitude of BMD accrual by abaloparatide,” the authors noted.
Summary and Clinical Applicability
In this study of postmenopausal women with osteoporosis, treatment with abaloparatide increased BMD in the lumbar spine, femoral neck, and total hip in a dose-dependent fashion.
“These data suggest that abaloparatide may have potential to provide protection against fractures consistently across a wide variety of ages and baseline risks, including those with and without prior fractures, as well as utility for a broad group of patients with osteoporosis,” the study authors concluded.
Radius Health, developer of abaloparatide, filed a new drug application for abaloparatide with the US Food and Drug Administration on March 30, 2016.
Limitations and Disclosures
These results were presented at the ENDO 2016, the annual meeting of the Endocrine Society, and have yet to undergo peer review prior to journal publication.
Radius Health funded this trial. Authors of this study disclosed relationships with Radius Health, Amgen, Eli Lilly, Merck, and Nordic Biosciences.
Cosman F, Hattersley G, Miller PD, et al. OR-1-2. Abaloparatide Significantly Reduces Vertebral and Nonvertebral Fractures and Increases BMD Regardless of Baseline Risk. Presented at: ENDO 2016; April 1-4, 2016; Boston, MA.