Literature DB >> 19890127

A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia.

Iain C Macdougall1, Jerome Rossert, Nicole Casadevall, Richard B Stead, Anne-Marie Duliege, Marc Froissart, Kai-Uwe Eckardt.   

Abstract

BACKGROUND: We investigated whether a novel, synthetic, peptide-based erythropoietin-receptor agonist (Hematide, Affymax) can stimulate erythropoiesis in patients with anemia that is caused by antierythropoietin antibodies.
METHODS: In this open-label, single-group trial, we enrolled patients with chronic kidney disease who had pure red-cell aplasia or hypoplasia due to antierythropoietin antibodies and treated them with a synthetic peptide-based erythropoietin-receptor agonist. The agonist was administered by subcutaneous injection at an initial dose of 0.05 mg per kilogram of body weight every 4 weeks. The primary end point was a hemoglobin concentration above 11 g per deciliter without the need for transfusions.
RESULTS: We treated 14 patients with the peptide agonist for a median of 28 months. The median hemoglobin concentration increased from 9.0 g per deciliter (with transfusion support in the case of 12 patients) before treatment to 11.4 g per deciliter at the time of the last administration of the agonist; transfusion requirements diminished within 12 weeks after the first dose, after which 13 of the 14 patients no longer required regular transfusions. Peak reticulocyte counts increased from a median of 10x10(9) per liter before treatment to peak counts of greater than 100x10(9) per liter. The level of antierythropoietin antibodies declined over the course of the study and became undetectable in six patients. One patient who initially responded to treatment had a diminished hematologic response a few months later despite increased doses of the agonist and required transfusions again; this patient was found to have antibodies against the agonist. One patient died 4 months after the last dose of the agonist, and a grade 3 or 4 adverse event occurred in seven other patients during the study period.
CONCLUSIONS: This novel agonist of the erythropoietin receptor can correct anemia in patients with pure red-cell aplasia caused by antierythropoietin antibodies. (ClinicalTrials.gov number, NCT00314795.). Copyright 2009 Massachusetts Medical Society.

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Year:  2009        PMID: 19890127     DOI: 10.1056/NEJMoa074037

Source DB:  PubMed          Journal:  N Engl J Med        ISSN: 0028-4793            Impact factor:   91.245


  44 in total

1.  Peginesatide and erythropoietin stimulate similar erythropoietin receptor-mediated signal transduction and gene induction events.

Authors:  Jennifer M Green; Karen Leu; Angela Worth; Richard B Mortensen; David K Martinez; Peter J Schatz; Don M Wojchowski; Peter R Young
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Journal:  Nat Rev Nephrol       Date:  2010-02-23       Impact factor: 28.314

5.  Interchangeability, immunogenicity and biosimilars.

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7.  Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients.

Authors:  Iain C Macdougall; Andrzej Wiecek; Beatriz Tucker; Magdi Yaqoob; Ashraf Mikhail; Michal Nowicki; Iain MacPhee; Michal Mysliwiec; Olgierd Smolenski; Władysław Sułowicz; Martha Mayo; Carol Francisco; Krishna R Polu; Peter J Schatz; Anne-Marie Duliege
Journal:  Clin J Am Soc Nephrol       Date:  2011-09-22       Impact factor: 8.237

8.  Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal Dialysis.

Authors:  Raja Zabaneh; Simon D Roger; Mohamed El-Shahawy; Michael Roppolo; Grant Runyan; Janet O'Neil; Ping Qiu
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9.  Peginesatide for maintenance treatment of anemia in hemodialysis and nondialysis patients previously treated with darbepoetin alfa.

Authors:  Steven Fishbane; Simon D Roger; Edouard Martin; Grant Runyan; Janet O'Neil; Ping Qiu; Francesco Locatelli
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Review 10.  HIF prolyl hydroxylase inhibitors for the treatment of renal anaemia and beyond.

Authors:  Patrick H Maxwell; Kai-Uwe Eckardt
Journal:  Nat Rev Nephrol       Date:  2015-12-14       Impact factor: 28.314

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