NCCN Recommends Rusfertide as Category 1 Option Across Low- and High-Risk Polycythemia Vera

Clinical Summary: 

• Guideline Update: Updated NCCN Guidelines for Myeloproliferative Neoplasms recommend rusfertide as a Category 1 treatment option across both low- and high-risk polycythemia vera, following its FDA approval for the treatment of erythrocytosis in adults with polycythemia vera. 
• Supporting Evidence: The recommendation was supported by the phase 3 VERIFY and phase 2 REVIVE studies. In VERIFY, rusfertide plus current therapy improved clinical response, hematocrit control, phlebotomy burden, and fatigue compared with placebo plus current standard-of-care therapy.
• Clinical Relevance: The NCCN recommendation incorporates hepcidin mimetic therapy into polycythemia vera management across risk groups, providing an additional strategy for maintaining hematocrit control and reducing reliance on therapeutic phlebotomy in patients with erythrocytosis.

Updated National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms recommend rusfertide (Mimrylo; Takeda) as a Category 1 treatment option across both low- and high-risk polycythemia vera.

The recommendation follows the US Food and Drug Administration (FDA) approval of rusfertide for the treatment of erythrocytosis in adults with polycythemia vera. Rusfertide is a first-in-class hepcidin mimetic designed to regulate iron distribution and reduce excess red blood cell production, thereby supporting hematocrit control.

Maintaining hematocrit below 45% is a primary treatment goal in polycythemia vera because uncontrolled erythrocytosis increases blood viscosity and the risk of thrombotic complications. Treatment has traditionally included phlebotomy and cytoreductive therapies, although some patients continue to experience inadequate hematocrit control and require repeated phlebotomy.

The NCCN recommendation was supported by findings from the phase 3 VERIFY and phase 2 REVIVE studies, which collectively evaluated more than 360 patients with polycythemia vera.

VERIFY is an ongoing, global, randomized, placebo-controlled phase 3 trial evaluating once-weekly subcutaneous rusfertide in 293 patients with uncontrolled hematocrit who remained dependent on phlebotomy despite current standard-of-care treatment, which could include phlebotomy, hydroxyurea, interferon, and/or ruxolitinib.

Patients received rusfertide plus their current therapy or placebo plus current standard-of-care therapy. The primary end point was clinical response during weeks 20 through 32, defined by the absence of phlebotomy eligibility.

Phlebotomy eligibility was defined as a confirmed hematocrit of at least 45% that was at least 3% higher than the patient's baseline value or a hematocrit of at least 48%.

Rusfertide plus current therapy produced a higher clinical response rate than placebo plus current therapy. Treatment also improved hematocrit control, reduced the need for phlebotomy, and improved fatigue as measured by the PROMIS Fatigue Short Form 8a. Symptom burden was additionally evaluated using the Myelofibrosis Symptom Assessment Form Version 4.0.

Rusfertide was generally well tolerated through 52 weeks of treatment in VERIFY. The most common treatment-emergent adverse events among rusfertide-treated patients were injection-site reactions and anemia.

The phase 2 REVIVE study provided additional evidence supporting the guideline recommendation. The trial evaluated rusfertide in adults with polycythemia vera across a dose-finding phase, a blinded placebo-controlled randomized withdrawal phase, and an open-label expansion.

Warnings and precautions for rusfertide include new or worsening thrombocytosis, injection-site reactions, and embryo-fetal toxicity. Because platelet counts may increase during treatment, complete blood counts should be monitored every 2 to 4 weeks following treatment initiation and during dose modifications, or as clinically indicated.

The most common adverse reactions were injection-site reactions, reported in 56% of patients, and anemia, reported in 16%.

Source: 

Takeda. Takeda’s rusfertide (MIMRYLO™) included as category 1 treatment for polycythemia vera in National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology for myeloproliferative neoplasms. Accessed on: September 22, 2026.  https://www.takedaoncology.com/newsroom/news-releases/2026/mimrylo-category-1-pv-nccn/