Eltrombopag: a powerful chelator of cellular or extracellular iron(III) alone or combined with a second chelator

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ELT is a powerful iron chelator, mobilizing iron and ferritin, reducing ROS, and restoring insulin production at clinically achievable levels. ELT enhances cellular iron chelation when combined with clinically available iron chelators through the shuttling of iron(III).

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Most cited references 48

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Hyperquad simulation and speciation (HySS): a utility program for the investigation of equilibria involving soluble and partially soluble species

Lucia Alderighi, Peter Gans, Andrea Ienco … (1999)

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Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.

Bhabita Mayer, Olga L Kovaleva, M Arning … (2007)

The pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) involves antibody-mediated platelet destruction and reduced platelet production. Stimulation of platelet production may be an effective treatment for this disorder. We conducted a trial in which 118 adults with chronic ITP and platelet counts of less than 30,000 per cubic millimeter who had had relapses or whose platelet count was refractory to at least one standard treatment for ITP were randomly assigned to receive the oral thrombopoietin-receptor agonist eltrombopag (30, 50, or 75 mg daily) or placebo. The primary end point was a platelet count of 50,000 or more per cubic millimeter on day 43. In the eltrombopag groups receiving 30, 50, and 75 mg per day, the primary end point was achieved in 28%, 70%, and 81% of patients, respectively. In the placebo group, the end point was achieved in 11% of patients. The median platelet counts on day 43 for the groups receiving 30, 50, and 75 mg of eltrombopag were 26,000, 128,000, and 183,000 per cubic millimeter, respectively; for the placebo group the count was 16,000 per cubic millimeter. By day 15, more than 80% of patients receiving 50 or 75 mg of eltrombopag daily had an increased platelet count. Bleeding also decreased during treatment in these two groups. The incidence and severity of adverse events were similar in the placebo and eltrombopag groups. Eltrombopag increased platelet counts in a dose-dependent manner in patients with relapsed or refractory ITP. (ClinicalTrials.gov number, NCT00102739.) 2007 Massachusetts Medical Society

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Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study.

Mansoor N Saleh, Graham Stone, Bhabita Mayer … (2011)

Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period. We undertook a phase 3, double-blind, placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30,000 per μL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count (≤ 15,000 per μL), use of treatment for immune thrombocytopenia, and splenectomy status. Patients, investigators, and those assessing data were masked to allocation. Dose modifications were made on the basis of platelet response. Patients were assessed for response to treatment (defined as a platelet count of 50,000-400,000 per μL) weekly during the first 6 weeks and at least once every 4 weeks thereafter; the primary endpoint was the odds of response to eltrombopag versus placebo. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00370331. Between Nov 22, 2006, and July 31, 2007, 197 patients were randomly allocated to treatment groups and were included in the intention-to-treat analysis (135 eltrombopag, 62 placebo). 106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8·2, 99% CI 3·59-18·73; p<0·0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p=0·016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p=0·001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild increases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients (vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag. Eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment. GlaxoSmithKline. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Author and article information

Journal

Title: Blood

Publisher: American Society of Hematology

ISSN (Print): 0006-4971

ISSN (Electronic): 1528-0020

Publication date Created: October 26 2017

Publication date (Print): October 26 2017

Volume: 130

Issue: 17

Pages: 1923-1933

Affiliations

[1 ]Haematology Department, University College London, London, United Kingdom;

[2 ]Institute of Pharmaceutical Science, King’s College London, London, United Kingdom;

[3 ]MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom;

[4 ]Paediatrics Department, Boston Children's Hospital, Boston, MA; and

[5 ]Haematology Department, Hammersmith Hospital, Imperial College London, London, United Kingdom

Article

DOI: 10.1182/blood-2016-10-740241

PMC ID: 6558288

PubMed ID: 28864815

SO-VID: 06d49ae7-b3a3-4c2d-9df4-17f0e7917633

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Eltrombopag: a powerful chelator of cellular or extracellular iron(III) alone or combined with a second chelator

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UCL: UN SDG 03 Good Health and Well-Being

Most cited references 48

Hyperquad simulation and speciation (HySS): a utility program for the investigation of equilibria involving soluble and partially soluble species

Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.

Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study.

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Cited by 39

Most referenced authors 756