Τίτλος:
Oral ferroportin inhibitor vamifeport for improving iron homeostasis and
erythropoiesis in beta-thalassemia: current evidence and future clinical
development
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: In beta-thalassemia, imbalanced globin synthesis causes
reduced red blood cell survival and ineffective erythropoiesis.
Suppressed hepcidin levels increase ferroportin-mediated iron transport
in enterocytes, causing increased iron absorption and potentially iron
overload. Low hepcidin also stimulates ferroportin-mediated iron release
from macrophages, increasing transferrin saturation (TSAT), potentially
forming non-transferrin-bound iron, which can be toxic. Modulating the
hepcidin-ferroportin axis is an attractive strategy to improve
ineffective erythropoiesis and limit the potential tissue damage
resulting from iron overload. There are no oral beta-thalassemia
treatments that consistently ameliorate anemia and prevent iron
overload.
Areas covered: The preclinical and clinical development of vamifeport
(VIT-2763), a novel ferroportin inhibitor, was reviewed. PubMed, EMBASE
and ClinicalTrials.gov were searched using the search term `VIT-2763'.
Expert opinion: Vamifeport is the first oral ferroportin inhibitor in
clinical development. In healthy volunteers, vamifeport had comparable
safety to placebo, was well tolerated and rapidly decreased iron levels
and reduced TSAT, consistent with observations in preclinical models.
Data from ongoing/planned Phase II studies are critical to define its
potential in beta-thalassemia and other conditions associated with iron
overabsorption and/or ineffective erythropoiesis. If vamifeport
potentially increases hemoglobin and reduces iron-related parameters, it
could be a suitable treatment for non-transfusiondependent and
transfusion-dependent beta-thalassemia.
Συγγραφείς:
Porter, John
Taher, Ali
Viprakasit, Vip
Kattamis, Antonis
and Coates, Thomas D.
Garbowski, Maciej
Durrenberger, Franz and
Manolova, Vania
Richard, Frank
Cappellini, M. Domenica
Περιοδικό:
Expert Review of Hematology
Εκδότης:
ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
Λέξεις-κλειδιά:
Ferroportin inhibitor; hepcidin; iron overload;
non-transfusion-dependent beta-thalassemia; transfusion-dependent
beta-thalassemia; vamifeport; VIT-2763
DOI:
10.1080/17474086.2021.1935854
