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.

2017-09-01·Cell1区 · 生物学

A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential

1区 · 生物学

Article

作者: Varani, Luca ; Espinosa, Diego A ; Lanzavecchia, Antonio ; Fibriansah, Guntur ; Foglierini, Mathilde ; Graham, Victoria ; Barca, Taylor ; Simonelli, Luca ; Broccoli, Vania ; Lok, Shee-Mei ; Stettler, Karin ; Ng, Thiam-Seng ; Jaconi, Stefano ; Harris, Eva ; Bardelli, Marco ; Shi, Jian ; Pedotti, Mattia ; Bianchi, Siro ; Pullan, Steven ; Pagani, Isabel ; Beltramello, Martina ; Dowall, Stuart ; Cameroni, Elisabetta ; Wang, Jiaqi ; Hewson, Roger ; Lim, Elisa X Y ; Zerbe, Oliver ; Rubio, Alicia ; Zatta, Fabrizia ; Jurt, Simon ; Cavalli, Andrea ; Sallusto, Federica ; Corti, Davide ; Vicenzi, Elisa

Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature. However, ZIKV escape mutants emerged in vitro and in vivo in the presence of ZKA190, as well as of other neutralizing mAbs. To counter this problem, we developed a bispecific antibody (FIT-1) comprising ZKA190 and a second mAb specific for DII of E protein. In addition to retaining high in vitro and in vivo potencies, FIT-1 robustly prevented viral escape, warranting its development as a ZIKV immunotherapy.

2016-01-01·BioMed Research International3区 · 生物学

Cost-Effectiveness between Double and Single Fecal Immunochemical Test(s) in a Mass Colorectal Cancer Screening

3区 · 生物学

ArticleOA

作者: Zhang, Su-Zhan ; Li, Qi-Long ; Huang, Yan-Qin ; Cai, Shan-Rong ; Zhu, Hong-Hong ; Zheng, Shu ; Ma, Xin-Yuan

This study investigated the cost-effectiveness between double and single Fecal Immunochemical Test(s) (FIT) in a mass CRC screening. A two-stage sequential screening was conducted. FIT was used as a primary screening test and recommended twice by an interval of one week at the first screening stage. We defined the first-time FIT as FIT1 and the second-time FIT as FIT2. If either FIT1 or FIT2 was positive (+), then a colonoscopy was recommended at the second stage. Costs were recorded and analyzed. A total of 24,419 participants completed either FIT1 or FIT2. The detection rate of advanced neoplasm was 19.2% among both FIT1+ and FIT2+, especially high among men with age ≥55 (27.4%). About 15.4% CRC, 18.9% advanced neoplasm, and 29.9% adenoma missed by FIT1 were detected by FIT2 alone. Average cost was $2,935 for double FITs and $2,121 for FIT1 to detect each CRC and $901 for double FITs and $680 for FIT1 to detect each advanced neoplasm. Double FITs are overall more cost-effective, having significantly higher positive and detection rates with an acceptable higher cost, than single FIT. Double FITs should be encouraged for the first screening in a mass CRC screening, especially in economically and medically underserved populations/areas/countries.

100 项与 FIT-1 相关的药物交易

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