Rusfertide Receives NCCN Category 1 Designation in Polycythemia Vera

Rusfertide (Mimrylo), a hepcidin mimetic therapy, is now recommended as a Category 1 treatment option across both low- and high-risk polycythemia vera (PV) in the NCCN Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms as of version 3.2026.¹ Rusfertide is the only treatment to receive this recommendation across both risk categories in the updated guidelines, following its recent FDA approval.

The update made as of September 18, 2026, states that subcutaneous rusfertide titrated to maintain hematocrit of under 45% “may be used instead of or in addition to cytoreductive therapy when frequent phlebotomy or phlebotomy intolerance is the indication.” It notes that rusfertide does not replace cytoreductive therapy when it is otherwise indicated, such as for control of leukocytosis, thrombocytosis, or other disease-related features.²

“The inclusion of [rusfertide] in the NCCN Guidelines is a meaningful milestone for patients with PV, who have long needed more options,” Rushi Potdar, MD, chief medical officer and head of global medical affairs, global oncology business unit at Takeda, stated in a news release. “[Rusfertide’s] availability in the US marks a potential shift in the treatment paradigm for PV, giving clinicians and patients access to a novel therapy with the potential to help maintain hematocrit control, which the majority of patients being treated for PV do not achieve today.”

Basis for the Guideline Update

The guideline inclusion was based on 2 late-stage pivotal studies enrolling more than 360 patients with PV: the phase 3 VERIFY trial (NCT05210790) and the phase 2 REVIVE trial (NCT04057040), both of which met key efficacy end points with a favorable safety profile.^3,4 In VERIFY, patients receiving rusfertide plus current therapy showed a higher response rate than those receiving placebo plus standard of care, including hematocrit control, reduced need for phlebotomy, and improvement in prespecified patient-reported outcomes for fatigue and symptom burden. Rusfertide was generally well tolerated through 1 year of treatment in VERIFY, with injection-site reactions and anemia being the most common treatment-emergent adverse events.

Regulatory Background for Rusfertide

The guideline update follows the FDA's August 28, 2026, approval of rusfertide for erythrocytosis in adults with PV,⁵ which was supported by VERIFY data showing that 76.9% of patients receiving rusfertide required no phlebotomies between weeks 20 and 32 of the study, compared with 32.9% of patients receiving placebo (P <.0001).³ Key secondary end points were also met, with hematocrit control below 45% achieved in 62.6% of patients receiving rusfertide compared with 14.4% receiving placebo (P <.0001), and a lower mean number of phlebotomies from weeks 0 to 32 with rusfertide vs placebo (0.5 vs 1.8, respectively; P <.0001).

Trial Design

VERIFY is an ongoing, 3-part, global, placebo-controlled trial now in its 156th week of evaluation, with an open-label extension available to participants still benefiting from treatment. Enrollment was limited to patients whose hematocrit remained uncontrolled and who continued to require phlebotomy despite standard-of-care management, whether that meant phlebotomy alone or in combination with hydroxyurea, interferon, or ruxolitinib (Jakafi). Response during weeks 20 through 32 served as the primary end point, measured based on whether patients no longer met criteria for phlebotomy eligibility, defined as a confirmed hematocrit at or above 45% that also represented at least a 3-percentage-point rise from baseline, or a hematocrit at or above 48% regardless of baseline.

Disease Background

PV is a chronic hematologic malignancy marked by erythrocytosis, leading to unchecked red blood cell production that increases blood viscosity and raises the odds of dangerous clotting complications, among them stroke, deep vein thrombosis, and pulmonary embolism. Clinical management of the disease centers on holding hematocrit under the 45% threshold to reduce the risk of thrombotic events and ease symptoms such as profound fatigue, itching, trouble concentrating, and night sweats.¹ Even so, roughly 4 in 5 patients continue to have uncontrolled hematocrit despite receiving phlebotomy, cytoreductive therapy, or both, and those whose hematocrit remains elevated face roughly quadruple the likelihood of a major cardiovascular event or cardiovascular death.

REFERENCES

1. 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. News release. Takeda. September 21, 2026. Accessed September 21, 2026. https://tinyurl.com/4d4cce3y

2. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 3.2026. Accessed September 22, 2026. https://tinyurl.com/27m47jep

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

4. Kremyanskaya M, Kuykendall AT, Pemmaraju N, et al. Rusfertide, a hepcidin mimetic, for control of erythrocytosis in polycythemia vera. N Engl J Med. 2024;390(8):723-735. doi:10.1056/NEJMoa2308809

5. FDA approves first drug of its kind for polycythemia vera, a rare blood disorder. News release. FDA. August 28, 2026. Accessed August 30, 2026. https://tinyurl.com/c56mh86y