Rusfertide

PTG-300, Mimrylo (reported US brand, 2026)

Cardiovascular & circulation

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Rusfertide completed Phase 3 and, according to news coverage, received FDA approval for polycythaemia vera on 28 August 2026 under the brand Mimrylo †. It is a specialist-prescribed medicine. Community or self-directed use is essentially none documented, though the mechanism (lowering iron availability and haematocrit) is occasionally discussed in endurance and testosterone-therapy forums; no such use has any evidence base.

Summary

Class: Synthetic hepcidin mimetic: an engineered cyclic peptide of around 20 amino acids (disulfide-bridged, with non-natural residues and a short lipid or PEG modification for stability) that reproduces the N-terminal activity of natural hepcidin †
Mechanism: Mimics hepcidin, the liver hormone that controls iron: it triggers degradation of ferroportin, trapping iron in gut cells and macrophages, which lowers the iron available to the bone marrow and so restrains red-cell overproduction
Routes studied: Subcutaneous injection, once weekly, self-administered
Half-life: Roughly 1–2 days †; weekly dosing relies on the durable effect on iron handling rather than continuous drug presence
Storage: Pre-filled syringes or vials, refrigerated per label †
Regulatory status: Reported FDA approval August 2026 for adults with polycythaemia vera †; not approved elsewhere as of review

Doses are as reported in studies or by the community — never recommendations.

1What it is

Hepcidin is a 25-amino-acid hormone made by the liver that acts as the body's iron thermostat. When hepcidin is high, iron is locked away; when it is low, iron floods into the blood and the bone marrow uses it to make red cells. Natural hepcidin is hard to use as a drug because it is cleared in minutes. Rusfertide is a re-engineered, stabilised version that keeps the key iron-regulating region and lasts long enough for weekly injection.

Polycythaemia vera (PV) is a chronic blood cancer driven almost always by a JAK2 mutation, in which the marrow makes too many red cells. The thickened blood raises the risk of clots and stroke. Standard care is repeated blood-letting (phlebotomy) to keep the haematocrit under 45%, plus aspirin, and cytoreductive drugs (hydroxyurea, interferon, ruxolitinib) for higher-risk patients. Phlebotomy works but causes iron deficiency, fatigue and poor concentration, and many patients still spend time above the 45% target. Rusfertide essentially induces a controlled, functional iron restriction that does the job of phlebotomy without removing blood.

2How it's thought to work

Rusfertide binds ferroportin, the only known cellular iron exporter, and causes it to be internalised and degraded, exactly as hepcidin does.

Iron absorbed from food stays in gut lining cells and is lost when they shed; iron recycled from old red cells stays inside macrophages. Serum iron and transferrin saturation fall within hours.

With less iron delivered to the marrow, erythropoiesis is limited and the haematocrit drifts down and stays controlled. Importantly, body iron stores (ferritin) actually rise because iron is retained in storage cells, so patients are not iron-deficient in the way phlebotomy makes them.

Platelets and white cells are not meaningfully affected, since the restriction is specific to the iron-hungry red-cell line.

A hepcidin mimetic. Hepcidin shuts ferroportin, the single gate iron leaves a cell by, so iron stays inside the cell instead of entering the blood — used to hold down red cell production in polycythaemia vera.Schematic — not to scale

3What the research shows

Phlebotomy-dependent polycythaemia vera

VERIFY randomised 293 patients with PV requiring frequent phlebotomy to weekly rusfertide or placebo on top of their existing therapy for 32 weeks. The primary endpoint, clinical response (no phlebotomy eligibility during weeks 20–32), was achieved by 76.9% versus 32.9% (p < 0.0001). Mean phlebotomies over 32 weeks were 0.5 versus 1.8; 62.6% versus 14.4% kept haematocrit below 45% throughout; patient-reported fatigue improved. In the open-label period 84.1% of responders maintained response to week 52 (presented at ASCO/EHA 2025 and ASH 2025; Kremyanskaya 2025, NEJM †). [2]

Graded A (small)

Phase 2

REVIVE, an open-label dose-finding study with a 12-week randomised withdrawal phase in 70 patients, showed that rusfertide essentially eliminated the need for phlebotomy and that haematocrit control was lost when patients were switched to placebo (Kremyanskaya 2024, NEJM). PACIFIC studied patients with high haematocrit †. [1]

Hereditary haemochromatosis

A small Phase 2 showed reduced transferrin saturation and reduced need for phlebotomy; this indication was deprioritised †.

4Reported side effects and interactions

Literature-reported

Injection-site reactions are the most common adverse event (around 47% in VERIFY, mostly mild erythema and pruritus). Anaemia (about 26%, reflecting the intended iron restriction overshooting), fatigue, pruritus, arthralgia, nausea. Serious adverse events were no more common than with placebo (3.4% vs 4.8%) and none was judged related to the drug; no grade 4 or 5 events. A 2023 clinical hold was placed briefly after non-clinical carcinogenicity studies in mice found benign and malignant skin tumours; it was lifted after review, and skin cancers in trials (basal and squamous cell) were examined closely with no clear excess established, but the label is expected to carry a note and recommend periodic skin examination †.

Community-reported

none documented.

Theoretical. iron restriction could in principle impair exercise capacity or cognition if over-applied; thrombotic risk is reduced by haematocrit control rather than increased, but this was not a trial endpoint.

Interactions. none established pharmacokinetically. Oral or IV iron supplements would directly oppose the mechanism; erythropoiesis-stimulating agents likewise.

Markers researchers commonly monitor

Per trial protocols and iron physiology:

Marker	Why it's watched
Haematocrit and haemoglobin	the primary efficacy and safety marker; target below 45%, avoid anaemia.
Ferritin and transferrin saturation	ferritin rises and transferrin saturation falls on treatment; the signature of a working hepcidin mimetic.
Full blood count including platelets and white cells	to confirm the effect is selective to red cells and to track underlying PV.
Skin examination	recommended because of the non-clinical skin tumour findings and the known skin-cancer risk from hydroxyurea in this population.
Patient-reported fatigue and concentration (e.g. MFSAF, PROMIS)	secondary outcomes that matter to patients.
JAK2 allele burden	tracked in PV research; rusfertide is not expected to change it.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied as a finished pharmaceutical for weekly self-injection into the abdomen or thigh after training, per the label; details of presentation to be confirmed on label publication †. No research form has documented community circulation. The calculator does not apply.

6Commonly studied alongside

Given on top of phlebotomy and, where used, hydroxyurea, interferon alfa or ruxolitinib. Compared indirectly with ropeginterferon alfa-2b (approved for PV). Related iron-axis peptides and mimetics: natural hepcidin (endogenous), minihepcidins (research), and the hepcidin-pathway agents in development for beta-thalassaemia.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Reported FDA-approved 28 August 2026 (Mimrylo) for adults with polycythaemia vera, after Priority Review and Breakthrough Therapy and Orphan Drug designations †
European Union	Not authorised; marketing authorisation application expected †
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport (WADA)	Not specifically listed. It lowers rather than raises haematocrit, so it is not a blood-doping agent; however, it may complicate Athlete Biological Passport interpretation. Check current list †

8Open questions

Does controlling haematocrit by iron restriction reduce thrombosis and progression to myelofibrosis as well as phlebotomy does? Long-term outcome data are not yet available.
The true magnitude of any skin-cancer signal.
Whether hepcidin mimetics will find use in haemochromatosis, thalassaemia or other iron-overload states.

9References

1Kremyanskaya M et al. (2024). Rusfertide, a hepcidin mimetic, for control of erythrocytosis in polycythemia vera (REVIVE). NEJM. PubMed · DOI
2Kremyanskaya M et al. (2025). Rusfertide for phlebotomy-dependent polycythemia vera: the VERIFY phase 3 trial. NEJM [verify authorship and journal]. PubMed
3Ganz T, Nemeth E (2012). Hepcidin and iron homeostasis. Biochim Biophys Acta. PubMed · DOI
4Casu C, Nemeth E, Rivella S (2018). Hepcidin agonists as therapeutic tools. Blood. PubMed · DOI
5Ginzburg YZ et al. (2021). Dysregulated iron metabolism in polycythemia vera: etiology and consequences. Leukemia [verify]. PubMed
6FDA approval announcement and prescribing information for rusfertide (2026) [verify]. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

forum threads →

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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