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

IF 3.1 3区医学 Q2 HEMATOLOGY

Current Opinion in Hematology Pub Date : 2023-03-01 Epub Date: 2022-12-29 DOI:10.1097/MOH.0000000000000747

Shivani Handa, Yelena Ginzburg, Ronald Hoffman, Marina Kremyanskaya

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引用次数: 0

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: Hepcidin agonists essentially serve as a 'chemical phlebotomy' and are poised to vastly improve the quality of life for phlebotomy requiring polycythemia vera patients.

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多发性红细胞症中的拟肝素：解决缺铁与红细胞增多症的矛盾。

综述的目的：在恢复多种血液病的铁稳态方面，开发血钙素疗法是一项突破性发现。治疗多发性红细胞症患者的拟肝素药物芦司非肽已进入后期临床开发阶段，目前正在进行全球 3 期试验[NCT05210790]。路斯非肽是第一个可能的非细胞再生治疗方案，可维持血细胞比容控制，避免对红细胞增多症患者进行抽血。在这篇综述中，我们讨论了红细胞增多症患者铁代谢失调的病理生物学问题，提供了以表皮素-铁蛋白轴为靶点的理论依据，并详细阐述了支持表皮素模拟物在红细胞增多症中发挥作用的临床前和临床试验证据：最近，鲁斯费肽（PTG300）的两项二期临床试验[NCT04057040 和 NCT04767802]的最新结果表明，该药物在消除治疗性抽血需求、使血液学参数正常化、补充铁储存以及缓解多血症患者的体征方面非常有效。小结：肝素激动剂实质上是一种 "化学抽血疗法"，有望大大改善需要进行抽血治疗的多发性红细胞增多症患者的生活质量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Hematology 医学-血液学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Hematology is an easy-to-digest bimonthly journal covering the most interesting and important advances in the field of hematology. Its hand-picked selection of editors ensure the highest quality selection of unbiased review articles on themes from nine key subject areas, including myeloid biology, Vascular biology, hematopoiesis and erythroid system and its diseases.