TY - JOUR
T1 - Hepcidin mimetics in polycythemia vera
T2 - resolving the irony of iron deficiency and erythrocytosis
AU - Handa, Shivani
AU - Ginzburg, Yelena
AU - Hoffman, Ronald
AU - Kremyanskaya, Marina
N1 - Funding Information:
We acknowledge grant support (P01 CA108671 (to R.H.); R56 DK132146-01 (to R.H. and Y.G.); and MPN Foundation (to Y.G.)) for this work.
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Purpose of reviewDevelopment of hepcidin therapeutics has been a ground-breaking discovery in restoring iron homeostasis in several haematological disorders. The hepcidin mimetic, rusfertide, is in late-stage clinical development for treating polycythemia vera patients with a global phase 3 trial [NCT05210790] currently underway. Rusfertide serves as the first possible noncytoreductive therapeutic option to maintain haematocrit control and avoid phlebotomy in polycythemia vera patients. In this comprehensive review, we discuss the pathobiology of dysregulated iron metabolism in polycythemia vera, provide the rationale for targeting the hepcidin-ferroportin axis and elaborate on the preclinical and clinical trial evidence supporting the role of hepcidin mimetics in polycythemia vera.Recent findingsRecently, updated results from two phase 2 clinical trials [NCT04057040 & NCT04767802] of rusfertide (PTG300) demonstrate that the drug is highly effective in eliminating the need for therapeutic phlebotomies, normalizing haematological parameters, repleting iron stores and relieving constitutional symptoms in patients with polycythemia vera. In light of these findings, additional hepcidin mimetic agents are also being evaluated in polycythemia vera patients.SummaryHepcidin agonists essentially serve as a 'chemical phlebotomy' and are poised to vastly improve the quality of life for phlebotomy requiring polycythemia vera patients.
AB - Purpose of reviewDevelopment of hepcidin therapeutics has been a ground-breaking discovery in restoring iron homeostasis in several haematological disorders. The hepcidin mimetic, rusfertide, is in late-stage clinical development for treating polycythemia vera patients with a global phase 3 trial [NCT05210790] currently underway. Rusfertide serves as the first possible noncytoreductive therapeutic option to maintain haematocrit control and avoid phlebotomy in polycythemia vera patients. In this comprehensive review, we discuss the pathobiology of dysregulated iron metabolism in polycythemia vera, provide the rationale for targeting the hepcidin-ferroportin axis and elaborate on the preclinical and clinical trial evidence supporting the role of hepcidin mimetics in polycythemia vera.Recent findingsRecently, updated results from two phase 2 clinical trials [NCT04057040 & NCT04767802] of rusfertide (PTG300) demonstrate that the drug is highly effective in eliminating the need for therapeutic phlebotomies, normalizing haematological parameters, repleting iron stores and relieving constitutional symptoms in patients with polycythemia vera. In light of these findings, additional hepcidin mimetic agents are also being evaluated in polycythemia vera patients.SummaryHepcidin agonists essentially serve as a 'chemical phlebotomy' and are poised to vastly improve the quality of life for phlebotomy requiring polycythemia vera patients.
KW - hepcidin mimetics
KW - myeloproliferative neoplasm
KW - polycythemia vera
KW - rusfertide
UR - http://www.scopus.com/inward/record.url?scp=85147783543&partnerID=8YFLogxK
U2 - 10.1097/MOH.0000000000000747
DO - 10.1097/MOH.0000000000000747
M3 - Review article
C2 - 36728649
AN - SCOPUS:85147783543
SN - 1065-6251
VL - 30
SP - 45
EP - 52
JO - Current Opinion in Hematology
JF - Current Opinion in Hematology
IS - 2
ER -