Overview1-3
Rusfertide is an investigational hepcidin mimetic which reduces iron availability for erythropoiesis, thereby controlling hematocrit.
Mechanism of Action2-8
Rusfertide is an investigational hepcidin-mimetic compound and a potential treatment for PV2.
Rusfertide functions in a similar way to the endogenous hormone hepcidin, systemically regulating iron export by:2,4
- Binding to and blocking the iron transporter ferroportin
- Inhibiting release of iron from the diet and from iron stores into plasma
- Reducing levels of serum iron and transferrin saturation
- Redistributing iron stores to reduce availability for erythropoiesis
Rusfertide induces internalization and degradation of ferroportin4,5
Clinical Trials
Study Name
Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)
CT.GOV ID
NCT04057040
Phase
Phase 2
Status
Active, not recruiting
View on ClinicalTrials.govStudy Name
A Phase 3 Study of Rusfertide in Patients With Polycythemia Vera (VERIFY)
CT.GOV ID
NCT05210790
Phase
Phase 3
Status
Active, not recruiting
References
1. Ginzburg Y, An X, Rivella S, Goldfarb A. Normal and dysregulated crosstalk between iron metabolism and erythropoiesis. Elife. 2023;12:e90189. Published 2023 Aug 14. doi:10.7554/eLife.90189
2. Kremyanskaya M, Kuykendall AT, Pemmaraju N, et al. Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera. N Engl J Med. 2024;390(8):723-735. doi:10.1056/nejmoa2308809
3. Modi NB, Shames R, Lickliter JD, Gupta S. Pharmacokinetics, pharmacodynamics, and tolerability of an aqueous formulation of rusfertide (PTG-300), a hepcidin mimetic, in healthy volunteers: A double-blind first-in-human study. Eur J Haematol. 2024;113(3):340-350. doi:10.1111/ejh.14243
4. Taranath R, Mattheakis L, Zhao L, et al. Mechanism of systemic iron regulation and hematocrit control by hepcidin peptidomimetics in pre-clinical models. 62nd Annual Meeting of the American Society of Hematology (ASH). 2020;136(1):49-50. doi:10.1182/blood-2020-141670
5. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122(2-3):78-86. doi:10.1159/000243791
6. Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M. Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci U S A. 2005;102(5):1324-1328. doi:10.1073/pnas.0409409102
7. Donovan A, Lima CA, Pinkus JL, et al. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metabolism. 2005;1(3):191-200. doi:10.1016/j.cmet.2005.01.003
8. Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007;18(2):394-400. doi:10.1681/asn.2006070802
