FDA Approves Rusfertide, First Hepcidin Mimetic for Polycythemia Vera

The FDA approved rusfertide (Mimrylo; Takeda Pharmaceuticals America), the first hepcidin-mimetic therapy for adults with polycythemia vera (PV) whose disease is not adequately controlled with existing treatments.

For pharmacists, the approval introduces a subcutaneous, self-injected agent that meaningfully reduces the need for therapeutic phlebotomy, a longstanding treatment burden, while improving hematocrit control in a disease defined by red blood cell overproduction and elevated cardiovascular risk.¹

A First-in-Class Mechanism

PV is a chronic myeloproliferative disorder in which the body overproduces red blood cells, thickening the blood and raising the risk of blood clots, stroke, and heart attack. A central goal of management is keeping hematocrit, the proportion of red blood cells in the blood, below 45% to reduce those cardiovascular risks, which often requires repeated phlebotomy.

Rusfertide is a first-in-class peptide that mimics hepcidin, the hormone that naturally regulates iron in the body. By limiting the iron available to make new red blood cells, rusfertide curbs their overproduction and helps keep red blood cell levels under control.^1,2

VERIFY Trial Results

The approval was supported by VERIFY (NCT05210790), a multicenter, randomized, double-blind, placebo-controlled phase 3 study of 293 adults with PV who required frequent phlebotomies despite ongoing standard-of-care therapy. Patients (median age, 57 years; 73.0% male) were randomized 1:1 to rusfertide or placebo over 32 weeks. Rusfertide began at 19 mg administered subcutaneously once weekly and was titrated to maintain hematocrit below 45%. Roughly 56% of patients in each arm received concurrent cytoreductive therapy.^1-3

On the primary end point, 76.9% of patients receiving rusfertide required no phlebotomies and did not meet phlebotomy eligibility criteria between weeks 20 and 32, compared with 32.9% on placebo (P < .0001). The mean number of phlebotomies across weeks 0 to 32 was 0.5 with rusfertide versus 1.8 with placebo (P < .0001), and more patients maintained hematocrit below 45% (62.6% vs 14.4%; P < .0001). Patients on rusfertide also showed statistically significant improvements in patient-reported fatigue on the PROMIS Fatigue SF-8a and in the MFSAF Total Symptom Score (P < .03).³

Safety and Pharmacist Considerations

The most common adverse reactions were injection site reactions and anemia; in VERIFY Part 1a, injection site reactions occurred in 55.9% of the rusfertide group versus 32.9% of the placebo group and anemia in 15.9% versus 4.1%. Serious adverse events occurred in 3.4% of patients on rusfertide and 4.8% on placebo, none considered related to rusfertide.^1,3

Because rusfertide is self-injected, pharmacists have a direct role in counseling patients on subcutaneous injection technique, site rotation to mitigate injection site reactions, and recognizing signs of anemia given the drug's iron-restricting mechanism. Adherence support and reinforcing the ongoing need for hematocrit monitoring during titration are also relevant touchpoints.

REFERENCES

1. FDA approves first drug of its kind for polycythemia vera, a rare blood disorder. News release. FDA. Released August 28, 2026. Accessed August 31, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-its-kind-polycythemia-vera-rare-blood-disorder

2. Rusfertide (Mimrylo) for the treatment of polycythemia vera. VERIFY (NCT05210790). ClinicalTrials.gov. Accessed August 31, 2026. https://clinicaltrials.gov/study/NCT05210790

3. Kuykendall AT, Pemmaraju N, Pettit KM, et al. Results from VERIFY, a phase 3, double-blind, placebo-controlled study of rusfertide for treatment of polycythemia vera (PV). J Clin Oncol. 2025;43(17_suppl):LBA3. doi:10.1200/JCO.2025.43.17_suppl.LBA3