Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis.

Shivani Handa, Yelena Ginzburg, Ronald Hoffman, Marina Kremyanskaya

Current opinion in hematology 2023 Mar 01

filter terms:

Development 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. Recently, 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. Hepcidin agonists essentially serve as a 'chemical phlebotomy' and are poised to vastly improve the quality of life for phlebotomy requiring polycythemia vera patients. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Shivani Handa, Yelena Ginzburg, Ronald Hoffman, Marina Kremyanskaya. Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis. Current opinion in hematology. 2023 Mar 01;30(2):45-52