FDA Approves Rusfertide to Treat Erythrocytosis In Polycythemia Vera

FDA has approved rusfertide, a groundbreaking therapy that promises to spare patients with polycythemia vera (PV) repeated phlebotomies, the agency and officials from Takeda and Protagonist Therapeutics announced in separate statements.^1,2

The late Friday action for rusfertide, to be sold as Mimrylo, marks the first approval for a hepcidin mimetic peptide in the treatment of adults with erythocytosis, a medical condition that causes abnormally elevated hematocrit levels in the blood. The approval is based on phase 3 data from the VERIFY trial (NCT05210790), which was presented during the plenary session at the American Society of Clinical Oncology (ASCO) annual meeting in 2025, a rare occasion for a study in PV.³

PV causes an overproduction of blood cells in a setting of systemic iron deficiency. As iron flows into the bone marrow, it causes an escalation of red cell production while depriving other tissues and organs of their needed iron supply. Thus, patients with PV experience both the fatigue caused by iron deficiency and the fallout of too many red blood cells, which cause bone pain and raise the risk of stroke, deep vein thrombosis, or pulmonary embolism. The standard of care has included repeated painful phlebotomies to remove excess blood, which studies show is costly to health systems and draining for patients’ quality of life.^3,4

“People living with polycythemia vera have long faced the challenge of managing a chronic blood disorder with frequent blood draws to help address the consequences of the red blood cell overproduction,” Tanya Wroblewski, MD, director of the Division of Nonmalignant Hematology within the FDA’s Center for Drug Evaluation and Research said in the agency’s statement. “Today's approval of [rusfertide] offers a new, first-in-class option that has the potential to meaningfully reduce patient burden.”¹

“For patients living with PV, uncontrolled hematocrit can have serious consequences, including an elevated risk of life-threatening thrombotic events," Andrew T. Kuykendall, MD, associate member in the Department of Hematology at Moffitt Cancer Center and lead investigator for VERIFY, said in the statement from Takeda.² “Current treatments, such as phlebotomy, leave a significant gap for too many patients and can pose challenges to daily life and routines. The approval of [rusfertide] offers clinicians and patients a novel, first-in-class therapy that targets erythrocytosis, which drives excess red blood cell production in PV.”

Repeat phlebotomies have always been an imperfect solution to excess blood cells in PV, because patients experience highs and lows in hematocrit levels that do damage to the body over time. By contrast, the mechanism of rusfertide is designed to allow patients to keep hematocrit in a consistent range, preventing both repeat phlebotomies and potentially long-range health problems.³

Rusfertide restores the body’s natural rhythms to regulate iron levels in the blood, allowing patients to maintain a steady hematocrit level, which is the percentage of red blood cells in the body’s overall supply—a healthy level is at or below 45%.

“When you control the iron in an optimal way, you are able to control the production of red blood cells. Typically, when hepcidin goes down, iron exchange into the bone marrow goes up,” Ramon Tiu, MD, now head and vice president, Oncology Clinical Sciences, Takeda Oncology, told The American Journal of Managed Care® in an interview during ASCO 2025.³

“The strength and consistency of the VERIFY data give me real confidence in [rusfertide’s] potential to advance how we treat PV in everyday practice and to maintain hematocrit control,” Kuykendall said in the statement.²

Results From VERIFY Lead to Approval

VERIFY involved 293 patients, randomized 1:1 to receive rusfertide (147 patents) or placebo (146 patients). Of the group, 73% were male, with a median 57 years of age (range, 27-86). In the 2 groups, 83 patients taking rusfertide (56.5%) and 81 taking placebo (55.5%) also received cytoreductive therapy. Rusfertide is self-administered through weekly subcutaneous injection.^3,5

The study’s primary efficacy end point was the share of patients achieving a clinical response and the absence of phlebotomies from weeks 20 to 32. Results showed 76.9% of the rusfertide group achieved this response, compared with 32.9% of the placebo group (P = .0001). In addition, only 27% of patients taking rusfertide required phlebotomies in weeks 0 to 32, compared with 78% who received placebo plus standard of care.^3,5

Data from an extension study presented in December 2025 at the American Society of Hematology showed that patients largely retained hematocrit control and avoided phlebotomy at 52 weeks.⁶

Other phase 3 data from VERIFY showed: ^3,5

• The mean number of phlebotomies per patient was 0.5 for the rusfertide group, compared with 1.8 in the placebo group. In the rusfertide group, this mean number was reduced across subgroups, including risk status and use of concurrent cytoreductive therapy, vs the placebo arm.
• 62.6% of patients in the rusfertide group maintained hematocrit levels below 45%, compared with 14.4% in the placebo group (P < .0001).
• Patients taking rusfertide showed statistically significant improvements in quality of life scores, across 2 different measures, the PROMIS Fatigue score and the Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score.

Adverse events (AEs) were generally low grade; these included localized injection site reactions (55.9%), anemia (15.9%), and fatigue (15.2%). Serious AEs occurred in 3.4% of the rusfertide arm and 4.8% of the placebo arm; however, none were considered related to rusfertide. Cancer was reported in 1 patient in the rusfertide arm (0.7%) and in 7 patients in the placebo arm (4.8%).^3,5

References

1. FDA approves first drug of its kind for polycythemia vera, a rare blood disorder. News. FDA. August 28, 2026. Accessed August 29, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-its-kind-polycythemia-vera-rare-blood-disorder
2. Takeda Receives U.S. FDA Approval of MIMRYLO™ (rusfertide), Marking a Potential Shift in the Treatment Paradigm for Polycythemia Vera. News release. Takeda. August 28, 2026. August 29, 2026. https://www.takeda.com/newsroom/newsreleases/2026/fda-approval-mimrylo/
3. Caffrey M. In VERIFY, rusfertide spares most patients with PV a phlebotomy for 32 weeks, improves QOL. 2025;31(Spec 8):SP498-SP499
4. Visweshwar N, Fletcher B, Jaglal M, et al. Impact of Phlebotomy on quality of life in low-risk polycythemia vera. J Clin Med. 2024;13(16):4952. doi:10.3390/jcm13164952.
5. 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):Abstract LBA3. doi:10.1200/JCO.2025.43.17_suppl.LBA3
6. Caffrey M. 52-Week VERIFY data show rusfertide brings sustained responses in PV. Am J Manag Care. 2026;32(Spec 1):SP36.