Rusfertide
A peptide that copies the hormone controlling iron traffic, approved to treat polycythaemia vera by starving red-cell production of its raw material
Polycythaemia vera makes too many red cells, and the standard answer has been to remove blood repeatedly. Rusfertide mimics hepcidin, locks iron inside the cells that store it, and leaves the marrow short of it. It was approved in 2026 as Mimrylo.
What is it?
Hepcidin controls iron's only exit from a cell: it binds ferroportin, the sole iron exporter, and has it degraded, so iron stays in gut cells and macrophages. Rusfertide copies that signal, leaving the marrow short of the iron it needs to build red cells — the point in a disease defined by building too many.
The trial that made the case is REVIVE. Seventy patients with phlebotomy-dependent polycythaemia vera went through 28 weeks of dose-finding, then 59 were randomised to rusfertide or placebo for 12 weeks; beforehand they had averaged nearly nine phlebotomies a year.
A later study shows how fast the effect arrives. In 20 patients whose haematocrit was above 48% despite treatment, 40 mg twice weekly brought 85% below 45% by week 8, with a median of 4.9 weeks to the first reading under 45%. Nobody needed a phlebotomy while on treatment.
The same mechanism was tried in the opposite disease, HFE-related haemochromatosis, where too little hepcidin lets iron build up: a phase 2 trial gave 10 mg weekly for 24 weeks. The approved indication is polycythaemia vera only.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Half-Life: How Much Remains
The dataset records a half-life of 28.6 ± 11.3 hours (mean plasma elimination) for Rusfertide. After each half-life, half of what was in the circulation is gone, so about 3% remains after five. Real clearance varies with the person, the dose, the route and kidney or liver function; this is arithmetic on a published figure, not a dosing tool.
Published Research
These are the trials that describe rusfertide, read from their PubMed abstracts: the phase 2 in polycythaemia vera, a rapid-control study, the haemochromatosis trial and a pharmacology study.
REVIVE, the phase 2
70 patients with phlebotomy-dependent polycythaemia vera entered 28 weeks of dose-finding; 59 were then randomised to rusfertide or placebo for 12 weeks. The endpoint combined haematocrit control, no phlebotomy and completing the regimen. Participants had averaged 8.7 phlebotomies a year beforehand.
How quickly it works
20 patients with haematocrit above 48% took 40 mg twice weekly until it fell below 45%, then weekly. By week 8, 85% were below 45% and 95% had fallen at least 5 points; the median time to the first reading under 45% was 4.9 weeks. No patient needed a phlebotomy during treatment.
The opposite disease
An open-label phase 2 trial at nine US and Canadian centres gave 10 mg weekly for 24 weeks to adults with HFE-related haemochromatosis on maintenance phlebotomy, keeping transferrin saturation under 40%.
What the body does with it
Healthy adults received 10 to 60 mg of the lyophilised formulation or a 20 mg prefilled syringe, crossover. Peak concentration came at 24 hours for lower doses and 2 to 4 hours at the top doses; terminal half-life ran from 19.6 to 57.1 hours.
Side Effects & Contraindications
Reported Side Effects
From the trials above and the Mimrylo label.
Contraindications & Cautions
A prescription drug for a disease managed by haematologists.
Legal Status
Rusfertide is approved in the US as Mimrylo.
Frequently Asked Questions
?What is rusfertide?
A synthetic peptide that mimics hepcidin, the hormone controlling iron traffic. It binds ferroportin so iron stays locked inside cells instead of reaching the blood.
?What is it approved for?
Erythrocytosis in adults with polycythaemia vera, as Mimrylo. The label starts at 19 mg weekly under the skin, within a 9.5 to 108 mg range.
?Does it replace phlebotomy?
That is the aim. In a later study no patient needed a phlebotomy while on treatment.
?Why does restricting iron help?
The marrow cannot build red cells without iron. Rusfertide leaves the JAK2-driven clone alone and removes its raw material.
References
- [fda-pi] Mimrylo (rusfertide) for injection Prescribing Information, sections 1 and 2. Takeda Pharmaceuticals America (DailyMed version 2, effective August 28, 2026; read September 30, 2026).
- [pubmed] Kremyanskaya M, et al. "Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera." N Engl J Med, 2024;390(8):723-735. PMID: 38381675.
- [pubmed] Chew LP, et al. "Rusfertide rapidly decreases hematocrit in patients with suboptimally controlled polycythemia vera." Leuk Res, 2025;159:108132. PMID: 41175501.
- [pubmed] Kowdley KV, et al. "Rusfertide for the treatment of iron overload in HFE-related haemochromatosis: an open-label, multicentre, proof-of-concept phase 2 trial." Lancet Gastroenterol Hepatol, 2023;8(12):1118-1128. PMID: 37863080.
- [pubmed] Modi NB, et al. "Pharmacokinetics and Pharmacodynamics of Rusfertide, a Hepcidin Mimetic, Following Subcutaneous Administration of a Lyophilized Powder Formulation in Healthy Volunteers." Drugs R D, 2024;24(4):539-552. PMID: 39546273.
- [pubmed] Modi NB, et al. "Evaluation of Rusfertide, a Hepcidin Mimetic, on Cardiac Repolarization: A Randomized, Placebo- and Positive-Controlled Crossover Thorough QT Study in Healthy Participants." Clin Ther, 2025;47(11):1043-1052. PMID: 41033871.
- [other] US FDA, Drugs@FDA (openFDA): MIMRYLO (rusfertide), Takeda, NDA 220605, prescription, powder in 9.5, 28, 41 and 54 mg base vials. Read September 30, 2026.
Sources & Citations
Studies were read from PubMed; indication, dose and half-life come from the Mimrylo label, read September 30, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.