What Is Rusfertide?
Published Oct 15, 2026 · 12 minute read
Rusfertide is a lab-made peptide that copies hepcidin, the hormone that decides how much iron the body releases into the blood. By starving the bone marrow of iron, it slows red blood cell production. The FDA approved it as Mimrylo in August 2026 for adults with polycythemia vera, and in its phase 3 trial about three in four patients stayed below the threshold for phlebotomy late in treatment, compared with one in three on placebo.
Key Takeaways
- Rusfertide is a synthetic peptide that imitates hepcidin, the hormone that limits how much iron enters the blood. Less available iron means fewer new red blood cells.
- The FDA approved it as Mimrylo on August 28, 2026, for erythrocytosis in adults with polycythemia vera. No other use is approved.
- In the 293-patient VERIFY trial, 76.9% of rusfertide patients met the response definition versus 32.9% on placebo, and phlebotomies over 32 weeks fell from 1.82 to 0.53 on average.
- The labeled warning is a rise in platelet counts. Injection-site reactions and anemia were also more common than with placebo.
- Testosterone lowers hepcidin, but no trial has tested rusfertide for testosterone-related high hematocrit. That use would be off-label and unstudied.
- The useful measurements are the ones the label relies on: a complete blood count every 2–4 weeks after starting and during dose changes.
Most drugs that change red blood cell counts act on the marrow directly. Epoetin alfa, for example, is a version of the hormone erythropoietin that pushes red cell production up. Rusfertide works on the supply side instead: it controls the iron that red cells need, and it pushes production down.
That makes it relevant beyond its narrow approval mainly as a question. People whose hematocrit climbs on testosterone often ask whether an iron-limiting drug could help them. The short answer is that it has never been tested for that, and this article explains why the gap matters.
| Rusfertide at a glance | What to know |
|---|---|
| Other names | Mimrylo (brand); PTG-300 (development code) |
| Class | Hepcidin mimetic; synthetic cyclic peptide |
| Developers | Protagonist Therapeutics; marketed by Takeda |
| US status | Prescription drug, approved August 28, 2026; no DEA schedule listed |
| Approved use | Erythrocytosis in adults with polycythemia vera |
| Route | Subcutaneous injection once a week |
| Half-life | 28.6 ± 11.3 hours after one 19 mg dose in healthy participants (label) |
| WADA | Not named on the 2026 Prohibited List |
| Main evidence gap | No data outside polycythemia vera and hemochromatosis, including testosterone-related high hematocrit |
1. How does rusfertide work?
Cells that release iron into the blood do so through an exit protein called ferroportin. Hepcidin shuts that exit. In Nemeth and colleagues’ cell experiments, hepcidin attached to ferroportin, which was then drawn inside the cell and broken down, stopping iron release.
Rusfertide imitates that action. The Mimrylo prescribing information describes it as blocking ferroportin so less iron is available to make red cells, which in turn lowers hematocrit, the percentage of blood volume taken up by red cells.
Chemically, it is a short peptide closed into a ring by a disulfide bond, with a palmitoyl group (a fatty-acid chain) attached. The product is the acetate salt, supplied as a freeze-dried powder with its own diluent, according to the label.
Why limit iron instead of removing blood?
Polycythemia vera (PV) is a bone marrow cancer, classed as a myeloproliferative neoplasm, driven by a JAK2 mutation that keeps red cell production switched on, as a 2026 review by Gendrot and colleagues summarizes. The main treatment target is a hematocrit under 45%, according to Takeda’s approval announcement.
The standard tool is phlebotomy, the medical removal of blood, sometimes with drugs that slow the marrow. Many patients end up short of iron, from repeated phlebotomy and other causes, while their marrow still overproduces red cells. The same review links that iron shortage to fatigue. Rusfertide aims to cap production at the source rather than draining blood after the fact.
One consequence shows up in stored iron. In VERIFY, average ferritin in the rusfertide group went from 21 mcg/L at the start to 174 mcg/L by week 52, per the label. Iron was being kept in storage rather than spent on new red cells.
2. What did the clinical trials show?
All controlled efficacy data come from people with PV. The published studies were funded by Protagonist Therapeutics or included its employees as authors.
VERIFY: the phase 3 trial
VERIFY randomized 293 adults with PV who still needed frequent phlebotomy despite standard care. Participants received rusfertide or placebo on top of their usual treatment for 32 weeks. Mean age was 57, and 73% were men. A responder was someone who never qualified for phlebotomy between weeks 20 and 32, as defined in the prescribing information.
| VERIFY outcome (32 weeks) | Placebo, n = 146 | Rusfertide, n = 147 |
|---|---|---|
| Responders, weeks 20–32 | 32.9% | 76.9% |
| Average phlebotomies, weeks 0–32 | 1.82 | 0.53 |
| Hematocrit held under 45% throughout | 14.4% | 62.6% |
| Change in PROMIS fatigue score | +0.19 | −1.79 |
Every difference in the table was statistically significant, with p under 0.0001 for the first three and p = 0.0252 for fatigue. The label does not report blood clots, strokes or survival, so the trial shows control of blood counts rather than proof of fewer complications.
Earlier and smaller studies
| Study | Who | Design | Main finding |
|---|---|---|---|
| REVIVE, Kremyanskaya et al., 2024 | 70 phlebotomy-dependent PV patients | 28-week open-label phase, then 12-week randomized withdrawal in 59 | Estimated phlebotomies per year fell from 8.7 to 0.6; in the withdrawal phase, 60% on rusfertide responded vs 17% on placebo |
| Chew et al., 2025 | 20 PV patients with baseline hematocrit above 48% | Open-label, no control group | 85% under 45% by week 8; 7 of 20 stopped treatment |
| Kowdley et al., 2023 | 16 people with HFE hemochromatosis | Open-label phase 2, no control group | Phlebotomies over 24 weeks fell from 2.31 to 0.06 on average; not an approved use |
The uncontrolled studies cannot separate the drug’s effect from other changes in care. REVIVE’s withdrawal phase and VERIFY carry the most weight because they compared rusfertide with placebo.
3. Is rusfertide FDA-approved?
Yes, for one indication. Drugs@FDA lists NDA 220605 as approved on August 28, 2026, as a new molecular entity with priority review and orphan status. Earlier that year, the FDA accepted the application and granted Priority Review, as Takeda reported in March 2026. The drug already held Breakthrough Therapy, Orphan Drug and Fast Track designations.
The approval covers erythrocytosis in adults with PV. Outside the US, Takeda says only that it is working with other regulators and names no further approvals. In sport, rusfertide does not appear on the WADA 2026 Prohibited List.
4. How is rusfertide dosed?
The figures below are the labeled regimen for PV, given for reference only. They come from the Mimrylo label.
| Labeled item | Detail |
|---|---|
| Starting dose | 19 mg subcutaneously once a week |
| Weekly range | 9.5–108 mg |
| Vial strengths | 9.5, 19, 28, 41 and 54 mg single-dose vials |
| Increases | One step at a time, after at least 2 weeks on the current dose, to reach or keep hematocrit under 45% |
| Decreases | One step for grade 2 or higher anemia or drug-related grade 3 or higher toxicity; stop if this occurs at 9.5 mg |
| Doses above 54 mg | Given as two injections; above 82 mg, split between day 1 and day 4 or 5 |
| Contraindications | None listed |
This step-by-step approach is a form of dose titration, guided by blood counts rather than by symptoms.
How long does it last?
| Pharmacokinetic measure (label) | Value |
|---|---|
| Time to peak, 19 mg | Median 24 hours (range 4–48) |
| Bioavailability by injection | About 51% |
| Half-life, 19 mg in healthy participants | 28.6 ± 11.3 hours |
| Steady state with weekly dosing | After about 3 doses |
| Protein binding | Over 99% |
The drug’s effect on iron outlasts its blood levels. After single doses in healthy people, serum iron dropped most at 24–48 hours, and the 41 mg and 54 mg doses kept it down for up to 96 hours, per the label. The first-in-human study by Modi and colleagues found that serum iron and transferrin saturation fell in proportion to dose across single doses of 1–80 mg.
A half-life model can sketch how drug levels decline between weekly injections. It cannot show iron restriction or hematocrit, which only a blood test measures.
5. Could rusfertide help with high hematocrit on testosterone?
This is the most common off-label question, and the evidence does not answer it. The biology is relevant: testosterone raises red cell production partly by lowering hepcidin.
| Study | Model | What happened to hepcidin |
|---|---|---|
| Bachman et al., 2014 | Older men on testosterone gel for 6 months | Fell at 1 and 3 months alongside higher erythropoietin, then drifted back by 6 months while hematocrit stayed up |
| Hennigar et al., 2020 | 50 young men in a 28-day severe energy deficit, 200 mg/week testosterone enanthate or placebo | 41% lower with testosterone than placebo |
| Guo et al., 2013 | Mice engineered to over-express hepcidin (animal data) | Testosterone’s hemoglobin rise was blunted |
| Guo et al., 2020 | Mice lacking hepcidin (animal data) | Testosterone still raised hematocrit, so hepcidin suppression was not essential |
Taken together, hepcidin is one contributor alongside a higher erythropoietin set point, not the whole mechanism. The Endocrine Society guideline treats hematocrit above 54% on testosterone as erythrocytosis and recommends pausing therapy, then resuming at a lower dose; it also notes phlebotomy works. A 2024 review by Bond and colleagues argued that even the evidence for phlebotomy in this setting is thin.
What is missing is any rusfertide trial in testosterone users. As of mid-October 2026, every study on ClinicalTrials.gov involves PV or hemochromatosis. The multiple-dose healthy-volunteer study, which gave 60 mg weekly for 5 weeks, confirmed that hemoglobin and hematocrit fell but was not designed to test any clinical benefit. Using rusfertide for testosterone-related erythrocytosis would be off-label, and its benefit and safety there are unknown.
6. What are the side effects and risks?
The label carries no boxed warning. These reactions occurred at least 5 percentage points more often than with placebo during VERIFY’s 32-week randomized phase, according to the prescribing information.
| Adverse reaction | Rusfertide, n = 145 | Placebo, n = 146 |
|---|---|---|
| Injection-site reactions | 56% | 33% |
| Anemia | 16% | 4.1% |
| High platelet count (thrombocytosis) | 8% | 0.7% |
| Shortness of breath (dyspnea) | 8% | 1.4% |
Platelets: the labeled warning
Platelet counts climbed by an average of 31% within the first 4 weeks. In 36% of patients they passed 600 × 10⁹/L, and in 6% they passed 1,000 × 10⁹/L, generally leveling off by week 8. The label’s response is blood counts every 2–4 weeks early on and during dose changes, with possible adjustments to rusfertide or to other PV drugs.
Anemia and injection sites
Anemia is the expected downside of restricting iron for red cells. Across 285 exposed patients followed for a median of 61 weeks, 11% needed a dose reduction for an adverse reaction, mostly anemia. Injection-site reactions, most often redness, itching and pain, led 0.7% of VERIFY patients to stop.
Pregnancy, breastfeeding and fertility
In animal studies, rusfertide caused malformations in rats and fetal loss in rabbits at exposures below the maximum human dose. The label calls for pregnancy testing, effective contraception and no breastfeeding during treatment and for at least 30 days after the last dose. In rats, fertility and sperm measures were unaffected.
Antibodies
About a third (34%) of VERIFY patients developed antibodies to the drug, roughly a third of them neutralizing, and the label reports 12% cross-reacting with natural hepcidin. The label found no apparent effect on drug levels, efficacy or safety.
7. Interactions and use with GLP-1 drugs
In laboratory testing described in the label, rusfertide neither inhibited nor induced the major CYP450 liver enzymes and was not a substrate or inhibitor of common drug transporters. It did not cause clinically significant QTc prolongation, a heart-rhythm measure. Severe liver impairment has not been studied.
No study has paired rusfertide with semaglutide, tirzepatide or other GLP-1 drugs. None of the sources reviewed here report effects on body weight or muscle. Anyone prescribed both should have the combination reviewed by the prescriber.
8. What can you meaningfully measure or track?
Rusfertide’s effect and its main risks both appear in a standard complete blood count (CBC). Hematocrit shows whether the drug is working, hemoglobin flags anemia, and the platelet count tracks the labeled warning. Ferritin reflects the shift of iron into storage seen in the trials.
For a useful record, log each weekly dose and injection site next to the date and result of each CBC. Because the label adjusts doses one step at a time based on hematocrit, a clear timeline of dose changes and lab values helps a clinician see the pattern. Note fatigue, shortness of breath and injection-site reactions too, since these were among the trial outcomes and side effects.
A log cannot replace the labeled monitoring schedule, and it cannot show whether rusfertide prevents clots or other PV complications, a question the label does not answer. The peptide tracking guide covers ways to keep doses, labs and symptoms together.
9. Rusfertide FAQ
What is rusfertide used for?
Its only approved use is treating erythrocytosis, meaning too many red blood cells, in adults with polycythemia vera. It was also studied in hereditary hemochromatosis, but that use is not approved.
Is rusfertide FDA-approved?
Yes. The FDA approved it under the brand name Mimrylo on August 28, 2026, after a priority review. It is a prescription drug, and Takeda's announcement names no approvals outside the US.
Can rusfertide lower hematocrit from testosterone?
This has not been studied. Testosterone does suppress hepcidin, which is part of how it raises red cell production, but every registered rusfertide trial is in polycythemia vera or hemochromatosis. Any such use would be off-label, with unknown benefit and safety.
What are the side effects of rusfertide?
In VERIFY, injection-site reactions, anemia, high platelet counts and shortness of breath occurred more often than with placebo. Platelet counts rose by an average of 31% within the first 4 weeks, which is why the label calls for regular blood counts.
How long does rusfertide stay in your system?
The label reports a half-life of 28.6 ± 11.3 hours after a single 19 mg dose in healthy participants. Its effect on serum iron lasted longer, up to 96 hours after the higher single doses tested.
Can rusfertide be used with semaglutide or tirzepatide?
No study has examined rusfertide alongside GLP-1 drugs. In laboratory tests it did not inhibit or induce the main liver enzymes that metabolize drugs, but that does not replace clinical data. A prescriber should review any combination.
Is rusfertide banned in sport?
Rusfertide is not named on the WADA 2026 Prohibited List. Athletes should still check current rules with their anti-doping organization.
Is rusfertide the same as hepcidin?
No. It is a synthetic, ring-shaped peptide with a fatty-acid side chain that copies hepcidin's action on the iron exporter ferroportin. The label reports that some anti-drug antibodies seen in trials, 12%, cross-reacted with natural hepcidin.
10. Sources
References used for this article
- FDA / DailyMed: Mimrylo (rusfertide) prescribing information
- FDA: Drugs@FDA, NDA 220605, Mimrylo
- Takeda (August 28, 2026): FDA approval of Mimrylo
- Takeda (March 2, 2026): NDA accepted with Priority Review
- Kremyanskaya et al. (2024): REVIVE phase 2 trial of rusfertide in polycythemia vera
- Chew et al. (2025): Rusfertide in polycythemia vera with uncontrolled hematocrit
- Modi et al. (2024): First-in-human single-dose study in healthy volunteers
- Modi et al. (2025): Multiple-dose study in healthy subjects
- Kowdley et al. (2023): Phase 2 trial in HFE-related hemochromatosis
- Nemeth et al. (2004): Hepcidin binds ferroportin and triggers its internalization
- Gendrot et al. (2026): Iron balance and erythrocytosis review
- Bhasin et al. (2018): Endocrine Society testosterone therapy guideline
- Bachman et al. (2014): Testosterone raises erythropoietin and suppresses hepcidin in older men
- Hennigar et al. (2020): Testosterone suppresses hepcidin during energy deficit
- Guo et al. (2013): Hepcidin over-expression and testosterone in mice
- Guo et al. (2020): Hepcidin not essential for testosterone's effect on red cells in mice
- Bond et al. (2024): Phlebotomy for testosterone-induced erythrocytosis review
- ClinicalTrials.gov: Registered rusfertide studies
- WADA: 2026 Prohibited List