The FDA has approved rusfertide (Mimrylo) for the treatment of adult patients with polycythemia vera.1,2
The approval was supported by data from the phase 3 VERIFY trial (NCT05210790), along with data from the phase 2 REVIVE (NCT04057040) and phase 3 THRIVE (NCT06033586) studies.
Results from the 32-week analysis of part 1a of VERIFY showed that 76.9% of patients treated with rusfertide (n = 147) achieved a clinical response—defined as absence of phlebotomy eligibility with no phlebotomies from weeks 20 to 32—compared with 32.9% of patients who received placebo (n = 146; P < .0001).1-3
In the 52-week analysis, 84.1% of responders in the rusfertide arm (n = 113) experienced a continued response through week 52.4 Notably, responses were achieved by 77.9% of patients from the placebo arm who crossed over to receive rusfertide in part 1b from weeks 40 to 52 (n = 140).
“For patients living with polycythemia vera, uncontrolled hematocrit can have serious consequences, including an elevated risk of life-threatening thrombotic events," Andrew T. Kuykendall, MD, lead investigator of VERIFY and associate member in the Department of Hematology at Moffitt Cancer Center, stated in a news release.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 polycythemia vera. The strength and consistency of the VERIFY data give me real confidence in [rusfertide’s] potential to advance how we treat polycythemia vera in everyday practice and to maintain hematocrit control.”
Rusfertide is an injectable peptide mimetic of hepcidin, the master iron-regulatory hormone.3,4 By binding ferroportin, the agent restricts the availability of iron for erythropoiesis, thereby limiting red blood cell production and controlling erythrocytosis.
VERIFY was a 3-part, global, randomized, double-blind, placebo-controlled phase 3 study that enrolled 293 patients with polycythemia vera who had uncontrolled hematocrit and were phlebotomy dependent, despite standard-of-care therapy, with or without concurrent cytoreductive therapy.5
In Part 1a, during weeks 0 to 32, patients were randomly assigned 1:1 to receive once-weekly, self-administered subcutaneous rusfertide or placebo, in addition to their current standard of care. During the open-label, Part 1b in weeks 32 to 52, all patients received rusfertide plus standard of care. Part 2 was a long-term, open-label safety evaluation period.
The primary end point was the proportion of patients achieving a clinical response, defined as the absence of phlebotomy eligibility and no phlebotomies from weeks 20 to 32, along with completion of Part 1a. Key secondary end points assessed over weeks 0 to 32 included the mean number of phlebotomies, the proportion of patients maintaining hematocrit below 45%, and mean change from baseline at week 32 in the PROMIS Fatigue Short Form 8a T-score and the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Total Symptom Score.4
Rusfertide met the VERIFY primary end point and all 4 key secondary end points. The mean number of phlebotomies from weeks 0 to 32 was 0.5 with rusfertide compared with 1.8 with placebo (P < .0001), and more patients treated with rusfertide maintained hematocrit below 45% from weeks 0 to 32 vs placebo (62.6% vs 14.4%; P < .0001).
Patient-reported symptom measures also favored rusfertide, with improvements reported in disease-related symptoms including fatigue, early satiety, night sweats, problems with concentration, and itching. For the PROMIS Fatigue Short Form 8a T-score, a decline of 1.78 was observed at week 32 with rusfertide vs a 0.17 increase with placebo, indicating less fatigue. Response was durable: 61.9% of patients continuously treated with rusfertide maintained absence of phlebotomy eligibility from baseline to week 52.
Findings from the ASH 2025 presentation showed the most common treatment-emergent adverse effects (AEs) in rusfertide-treated patients comprised injection site reactions (47.4%), anemia (25.6%), and fatigue (19.6%); the majority were grade 1 or 2 in severity. Serious AEs occurred in 3.4% of patients treated with rusfertide and 4.8% of those given placebo, none of which were considered related to rusfertide. No grade 4 or 5 AEs were reported.
. News release. FDA. [Month Day], 2026. Accessed July 9, 2026.
