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Review of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed., Purpose: Abaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history., Methods: Data for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six academic and clinical practice settings across the US., Results: A total of 173 patients were enrolled (mean [SD] age, 69.8 [7.4] years). At the time of abaloparatide treatment initiation, 78.6% had received other osteoporosis medications. Mean (SD) time from discontinuation of osteoporosis medications prior to initiation of abaloparatide was 1.7 (3.2) years. Twenty-four months of follow-up data from the initiation date of abaloparatide was collected from 94.0% of patients and 6.0% of patients had 12-24 months of follow-up. During the follow-up period, 96.0% of patients had at least one visit for osteoporosis management and 55.5% had access to a medication support program. The median duration of therapy was 18.6 months and 105/162 (64.8%) completed abaloparatide treatment as prescribed. The most common reasons for treatment discontinuation were financial (31.2%) and tolerability (22.8%). Following completion of a course of treatment with abaloparatide, 82/162 (50.6%) patients transitioned to another osteoporosis medication. The median time between abaloparatide treatment course completion and the initiation of follow-on medication was 21 days., Conclusion: Most patients completed treatment with abaloparatide as prescribed, and over half continued with an antiresorptive agent. This favorable conduct may be the result of regular follow-up visits and accessibility to both medication and patient support services., (© 2024. The Author(s).)

Background: Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem., Methods: This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone., Results: Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18., Conclusions: Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA., Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: Yamei Wang and John I. Boxberger are employees of the study funder, Radius Health, Inc. Renaud Winzenrieth and Ludovic Humbert work for 3D-Shaper Medical and are paid consultants who conducted the analysis. Funding for this study and the parent ACTIVE trial was provided by Radius Health, Inc., and 2 authors are employees of Radius. In addition, 1 author is an employee of and stockholder in 3D-Shaper, which is a paid consultant to and analytical partner of Radius as well as the manufacturer of the software used in the study, and another is a former employee of 3D-Shaper. Medical writing support was provided by Paul Kostenuik, PhD (Phylon Pharma Services), and was funded by Radius. Medical editorial support (Lacy Miron, PharmD [assembling tables and figures, collating author comments, copyediting, fact checking, and referencing]) and graphic services were provided by AOIC, LLC, and were funded by Radius. The Article Processing Charge for open access publication was funded by Radius. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H991 )., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated.)

Real-World Evidence (RWE), which has historically been used to support post-approval safety studies, has recently gained acceptance for new drug applications as supportive evidence or as new clinical evidence for medicinal products with orphan designation and/or in disease areas with high unmet need. Here, we present a case study for the use of RWE in the approval of abaloparatide in the European Union (EU) under the tradename Eladynos. In addition to data from the pivotal Phase 3 study, the marketing authorization application (MAA) included clinical data from additional interventional and observational studies, as well as post-marketing data obtained from the United States (US) market since approval of abaloparatide by the Food and Drug Administration (FDA) in 2017. The new interventional studies were not designed to assess fracture efficacy and cardiovascular safety which were topics of concern raised by the Committee for Medicinal Products for Human Use (CHMP) during their review of the initial MAA submitted in 2015. However, these studies taken together with the RWE formed the basis for a new MAA. Prior to the planned resubmission in the EU, national Scientific Advice (SA) was sought on the proposed clinical program, specifically on the relevance of Real-World Data (RWD) derived from an observational study to support and complement the efficacy and safety data already available from prospective randomized clinical trials. This case study demonstrates successful use of RWE to address a previously identified gap raised by the CHMP during the review of an earlier MAA, which led to the approval of Eladynos for the treatment of osteoporosis in the EU., (© 2024. The Author(s).)

Context: Abaloparatide is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture., Objectives: We assessed the cardiovascular safety profile of abaloparatide., Design: Review of heart rate (HR), blood pressure (BP), and cardiovascular-related adverse events (AEs), including major adverse cardiovascular events (MACEs) and heart failure (HF) from: (a) ACTIVE (NCT01343004), a phase 3 trial that randomized 2463 postmenopausal women with osteoporosis to abaloparatide, teriparatide, or placebo for 18 months; (b) ACTIVExtend (NCT01657162), where participants from the abaloparatide and placebo arms received alendronate for 2 years; and (c) a pharmacology study in 55 healthy adults., Results: Abaloparatide and teriparatide transiently increased HR relative to placebo. Following first dose, mean (standard deviation [SD]) HR change from pretreatment to 1 hour posttreatment was 7.9 (8.5) beats per minute (bpm) for abaloparatide, 5.3 (7.5) for teriparatide, and 1.2 (7.1) for placebo. A similar pattern was observed over subsequent visits. In healthy volunteers, HR increase resolved within 4 hours. The corresponding change in mean supine systolic and diastolic BP 1 hour posttreatment was -2.7/-3.6 mmHg (abaloparatide), -2.0/-3.6 (teriparatide), and -1.5/-2.3 (placebo). The percentage of participants with serious cardiac AEs was similar among groups (0.9%-1.0%). In a post hoc analysis, time to first incidence of MACE + HF was longer with abaloparatide (P = 0.02 vs placebo) and teriparatide (P = 0.04 vs placebo)., Conclusions: Abaloparatide was associated with transient increases in HR and small decreases in BP in postmenopausal women with osteoporosis, with no increase in risk of serious cardiac AEs, MACE, or HF., (© Endocrine Society 2020.)

Purpose: Current treatment guidelines recommend treatment for postmenopausal women with a T score <2.5 regardless of age. This subgroup analysis evaluated the efficacy and safety of abaloparatide in younger postmenopausal women considered to be at high risk for fracture., Methods: Subgroup analysis of women in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial who were <65 years old and met modified utilization management criteria (baseline T score ≤-2.5 [any site] and ≥1 prevalent vertebral and/or ≥1 prior clinical fracture within 5 years of randomization)., Findings: A total of 296 women (age range, 49-64 years) were included. Significant increases in bone mineral density from baseline were observed for abaloparatide versus placebo at all 3 sites at 6 months (p < 0.01 for total hip and femoral neck; p < 0.0001 for lumbar spine), 12 months (p < 0.0001 at all 3 sites), and 18 months (p < 0.0001 at all 3 sites). Fracture rates were numerically lower for abaloparatide versus placebo, consistent with the overall trial results, although the differences were not statistically significant. The number needed to treat to prevent 1 additional vertebral fracture after 18 months of treatment versus placebo was 18 for abaloparatide and 21 for teriparatide. The number needed to treat had nonsignificant trends toward lower values with abaloparatide versus teriparatide for nonvertebral fractures (23 vs 40) and clinical fractures (16 vs 73) and similar for major osteoporotic fractures (24 vs 27). The safety profile was consistent with the overall ACTIVE population., Implications: Findings of this subgroup (post hoc) analysis are consistent with the overall ACTIVE population. Abaloparatide appears to be effective and well tolerated in this subgroup of younger postmenopausal women. ClinicalTrials.gov identifier: NCT01343004., Competing Interests: Disclosures Dr Saag is a consultant to Amgen, Eli Lilly, and Radius Health, Inc., and has received research support from Amgen and Eli Lilly and Company. Drs Williams, Wang, and Weiss are employees of and own company stock in Radius Health Inc. Dr Cauley and the other authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The US Food and Drug Administration has recently approved abaloparatide (ABL) for treatment of women with postmenopausal osteoporosis (PMO) at high risk of fracture. With increasing health care spending and drug prices, it is important to quantify the value of newly available treatment options for PMO., Objective: To determine cost-effectiveness of ABL compared with teriparatide (TPTD) for treatment of women with PMO in the United States., Methods: A discrete-event simulation (DES) model was developed to assess cost-effectiveness of ABL from the US health care perspective. The model included three 18-month treatment strategies with either placebo (PBO), TPTD, or ABL, all followed by additional 5-year treatment with alendronate (ALN). High-risk patients were defined as women with PMO ⩾65 years old with a prior vertebral fracture. Baseline clinical event rates, risk reductions, and patient characteristics were based on the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial., Results: Over a 10-year period, the DES model yielded average total discounted per-patient costs of $10 212, $46 783, and $26 837 and quality-adjusted life-years (QALYs) of 6.742, 6.781, and 6.792 for PBO/ALN, TPTD/ALN, and ABL/ALN, respectively. Compared with TPTD/ALN, ABL/ALN accrued higher QALYs at lower cost and produced an incremental cost-effectiveness ratio (ICER) of $333 266/QALY relative to PBO/ALN. In high-risk women, ABL/ALN also had more QALYs and less cost over TPTD/ALN and yielded an ICER of $188 891/QALY relative to PBO/ALN. Conclusion and Relevance: ABL is a dominant treatment strategy over TPTD. In women with PMO at high risk of fracture, ABL is an alternative cost-effective treatment.

Objective: Advanced age is an important risk factor for fracture. The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) trial showed that subcutaneous abaloparatide increased bone mineral density (BMD) and reduced the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. This study describes the effects of abaloparatide in the subgroup of women aged 80 or more years in ACTIVE., Methods: Post hoc analyses of BMD and fracture incidence in this subgroup of women who received abaloparatide or placebo in the 18-month, phase 3, double-blind, randomized controlled ACTIVE trial., Results: The mean ages of the women ≥80 years were 81.9 and 81.7 years in the placebo (n = 43) and abaloparatide (n = 51) groups, respectively. The increases in BMD from baseline to 18 months with abaloparatide treatment were 3.9% at the total hip (P < 0.001), 3.6% at the femoral neck (P < 0.01), and 12.1% at the lumbar spine (P < 0.001), and were similar to those observed in the overall population. Abaloparatide therapy was associated with numerical, but not statistically significant, reductions in the risk of vertebral and nonvertebral fractures in this subpopulation, compared with placebo. The proportion of participants reporting adverse events was similar between treatment groups and between the older subgroup and the overall population., Conclusion: Abaloparatide was effective in increasing BMD in the very elderly subgroup of ACTIVE, with a safety profile similar to that of the overall study population.

Geographic heterogeneity has been observed in fracture risk and efficacy of therapeutic intervention in postmenopausal osteoporosis. The objectives of these analyses were to assess across geographic and ethnic subgroups the heterogeneity of fracture incidence and baseline risk, and consistency of effect of abaloparatide-SC vs placebo on fracture risk reduction in the 18-month, phase 3, multinational, ACTIVE randomized controlled trial. Prespecified exploratory analyses of geographic subgroups (North America, South America, Europe, Asia) and post hoc analyses of ethnic subgroups (Hispanic or Latino, other) of postmenopausal women with osteoporosis enrolled in the abaloparatide-SC and placebo cohorts (n = 1645) were performed. Country-specific FRAX models were used to calculate 10-year absolute fracture risks. Relative risk reductions for vertebral fractures and hazard ratios for non-vertebral, clinical, and major osteoporotic fractures were calculated. Forest plots were constructed to assess treatment-by-subgroup interactions for each geographic region and ethnicity. Baseline prevalence of vertebral fractures was similar across geographies; baseline prevalence of non-vertebral fractures was more variable. Ten-year major osteoporosis fracture and hip fracture risks were variable across and within regions. The effects of abaloparatide-SC on reducing the risk of vertebral, non-vertebral, clinical, and major osteoporotic fractures were similar across regions, and for Hispanic or Latino vs other ethnicities. A limitation was the limited power to detect interactions with few events. In conclusion, despite geographic variability in fracture incidence and risk at baseline, no differences were detected in the effects of abaloparatide-SC in reducing vertebral, non-vertebral, clinical, and major osteoporotic fracture risk across assessed geographic regions and ethnicities.

There are a number of effective treatments for osteoporosis but most are in the antiresorptive class of compounds. Abaloparatide-SC is a new osteoanabolic agent, which increased bone mineral density and lowered the risk of osteoporosis-related fractures in the phase 3 ACTIVE trial. The objective of this report is to describe the effects of abaloparatide-SC 80μg on bone histology and histomorphometry in iliac crest bone biopsies from this trial in which participants were randomized to receive blinded daily subcutaneous injections of placebo or abaloparatide-SC 80μg/d or open-label teriparatide 20μg/d for 18months. Iliac crest bone biopsies were obtained between 12 and 18months. Qualitative histological analysis of biopsies from abaloparatide-SC-treated patients revealed normal bone microarchitecture without evidence of adverse effects on mineralization or on the formation of normal lamellar bone. There were no bone marrow abnormalities, marrow fibrosis nor was there presence of excess osteoid or woven bone. There were few significant differences among the three treatment groups in a standard panel of static and dynamic histomorphometric indices. The mineral apposition rate was higher in the teriparatide-treated group than in the placebo-treated group. The eroded surface was lower in the abaloparatide-SC-treated group than in the placebo-treated group. Cortical porosity was higher in both the abaloparatide-SC- and the teriparatide-treated groups than in the placebo-treated group. We conclude that histological and histomorphometric analysis of iliac crest bone biopsies from subjects who were treated for up to 18months with abaloparatide-SC showed no evidence of concern for bone safety., Trial Registration: ClinicalTrials.gov number NCT01343004., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80 μg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12 mo and/or a shift in T-score category (based on LS and TH T-scores) at 12 mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], P  = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], P  < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], P  < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12 mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study. [ABSTRACT FROM AUTHOR]