The NCCN has updated its Clinical Practice Guidelines in Oncology for myeloproliferative neoplasms (MPNs) to include rusfertide (Mimrylo) as a category 1 treatment option across both low- and high-risk polycythemia vera (PV), according to a news release from the developer, Takeda.¹ Rusfertide is the only treatment recommended as a category 1 option across both risk groups in the updated guidelines (version 3.2026), which were updated on September 18, 2026.
How do the updated NCCN guidelines recommend rusfertide?
In the low-risk PV setting, the guidelines state that subcutaneous rusfertide, titrated to maintain a hematocrit below 45%, may be used in place of or in addition to cytoreductive therapy when frequent phlebotomy or phlebotomy intolerance is the indication.² In the high-risk setting, rusfertide may be added to cytoreductive therapy for inadequate hematocrit control or a persistent phlebotomy requirement. In both settings, the guidelines specify that rusfertide does not replace cytoreductive therapy when cytoreduction is otherwise indicated, including for the control of leukocytosis, thrombocytosis, or other disease-related features.
What data supported the recommendation?
NCCN Guidelines inclusion was based on 2 late-stage pivotal studies that included more than 360 patients with PV: the phase 3 global, randomized VERIFY study (NCT05210790) and the phase 2 REVIVE study (NCT04057040). In VERIFY, patients receiving rusfertide plus current standard therapy demonstrated a higher response rate than those receiving placebo plus current standard of care, including hematocrit control, a reduction in the need for phlebotomy, and improvement in patient-reported fatigue as measured by the PROMIS Fatigue Short Form 8a and symptom burden as measured by the Myelofibrosis Symptom Assessment Form version 4.0. Rusfertide was generally well tolerated through 52 weeks in VERIFY, with the most common treatment-emergent adverse events including injection site reactions and anemia. “The inclusion of [rusfertide] in the NCCN Guidelines is a meaningful milestone for patients with PV, who have long needed more options,” said Rushi Potdar, MD, chief medical officer and head of global medical affairs, Global Oncology Business Unit, at Takeda, in the news release.¹ “[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.”
What is rusfertide, and what is its regulatory history?
Rusfertide is a first-in-class hepcidin mimetic administered once weekly via subcutaneous injection that is designed to regulate iron distribution and red blood cell overproduction to help control hematocrit. The FDA previously approved rusfertide in August 2026 for the treatment of adults with PV based on data from the VERIFY trial, in which 76.9% of patients treated with rusfertide did not require phlebotomy during the 32-week period compared with 32.9% of patients who received placebo.³
What is the unmet need in polycythemia vera?
PV is a chronic blood cancer characterized by the overproduction of red blood cells, which increases blood viscosity and can lead to thrombotic events such as stroke, deep vein thrombosis, and pulmonary embolism. Maintaining a hematocrit below 45% is the primary treatment goal to prevent thrombotic events and alleviate symptoms such as severe fatigue, pruritus, difficulty concentrating, and night sweats. According to the press release, an estimated 78% of patients still experience uncontrolled hematocrit despite treatment such as phlebotomy and cytoreductive therapies, and patients with uncontrolled hematocrit have a 4-times higher risk of cardiovascular death or major cardiovascular events.
References
- 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/ya2k7fws
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Myeloproliferative Neoplasms. Version 3.2026. National Comprehensive Cancer Network. September 18, 2026. Accessed September 21, 2026. https://tinyurl.com/3rfmv4np
- FDA approves first drug of its kind for polycythemia vera, a rare blood disorder. News release. FDA. August 28, 2026. Accessed September 21, 2026. https://tinyurl.com/yeavrkc4
