Rusfertide (Mimrylo) maintained clinical benefit vs placebo in patients with both low-risk and high-risk polycythemia vera (PV), according to a subgroup analysis of the phase 3 VERIFY trial (NCT05210790) presented in a poster session at the
Between weeks 20 and 32, the proportion of patients achieving a clinical response, defined as an absence of phlebotomy eligibility, was higher with rusfertide than with placebo across risk categories. Among patients with high-risk PV, 71.2% of those treated with rusfertide (n = 66) achieved a response vs 31.0% of those given placebo (n = 71; P < .0001). Among patients with low-risk disease, the respective rates were 80.2% (n = 81) vs 34.7% (n = 75; P < .0001). Overall, 76.2% of rusfertide-treated patients (n = 147) responded vs 32.9% of those given placebo (n = 146; P < .0001).
“These results demonstrate that the benefit of rusfertide was maintained for the primary end point of clinical response and all key secondary end points of reduction in phlebotomies and hematocrit control vs placebo, irrespective of whether patients had low-risk or high-risk PV at baseline,” lead study author Naveen Pemmaraju, MD, and colleagues wrote in the poster.
Pemmaraju is a professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.
In August 2026,
VERIFY is an ongoing, 3-part, global, randomized, double-blind, placebo-controlled phase 3 study evaluating rusfertide, a first-in-class, self-administered subcutaneous peptide mimetic of the hormone hepcidin, added to current standard-of-care (CSC) therapy.1 The trial enrolled 293 patients with PV who had inadequately controlled hematocrit and required frequent phlebotomy despite CSC, defined as phlebotomy with or without cytoreductive therapy (CRT).
In Part 1a, patients were randomly assigned 1:1 to once-weekly rusfertide or placebo, each added to CSC, with the treatment period comprising baseline to week 32; thereafter, all patients were eligible to receive rusfertide during the open-label parts of the study.
The primary end point was the proportion of patients achieving a clinical response, and key secondary end points included mean number of phlebotomies, the proportion of patients with hematocrit below 45%, and patient-reported outcomes (PROs).
This post hoc analysis, with a data cutoff of December 10, 2025, evaluated outcomes by risk category and by concurrent CRT status. Low-risk PV was defined as age younger than 60 years with no thromboembolic events (TEs) prior to study entry, and high-risk PV was defined as age 60 years or older and/or a TE prior to study entry.
In the overall study population across both arms, 156 patients (53.2%; median age, 52.0 years) had low-risk PV and 137 (46.8%; median age, 66.0 years) had high-risk PV, and the median duration of rusfertide exposure was 88.1 weeks (range, 2-158).
Among high-risk patients receiving concurrent CRT, 72.0% patients treated with rusfertide (n = 50) responded vs 32.7% patients given placebo (n = 52), with comparable proportions among low-risk patients receiving concurrent CRT (71.9% [n = 32] vs 32.1% [n = 28]).
Between baseline and week 32, there were 35 total phlebotomies in the rusfertide arm compared with 251 in the placebo arm, with improvements observed irrespective of risk group or concurrent CRT use. Among patients receiving concurrent CRT, the mean number of phlebotomies was lower with rusfertide than with placebo in both the high-risk group (0.64 [SD, 1.45] vs 1.77 [SD, 1.52]) and the low-risk group (0.34 [SD, 0.74] vs 2.0 [SD, 1.35]).
In high-risk patients receiving concurrent CRT, 60.0% given rusfertide maintained a hematocrit below 45% vs 15.4% of those treated with placebo (nominal P < .0001), with a similar proportion seen among low-risk patients receiving concurrent CRT (59.4% vs 10.7%; nominal P = .0002).
Numeric improvements in the PROMIS Fatigue Short Form 8a T-score and the Myelofibrosis Symptom Assessment Form v4.0 Total Symptom Score-7 at week 32 were also observed with rusfertide vs placebo in both risk groups.
As of the December 10, 2025, data cutoff, the incidence of treatment-emergent adverse effects (TEAEs) in rusfertide-treated patients (n = 291) was similar in the high-risk (96.1%) and low-risk (94.2%) PV groups, and the majority of TEAEs were mild to moderate in severity. Grade 3 or 4 TEAEs occurred in 27.1% of high-risk and 17.3% of low-risk patients, and no grade 5 TEAEs were reported. Serious AEs were reported in 14.7% of patients with high-risk PV vs 6.4% of patients with low-risk PV, and there were no deaths on study in either risk group. TEAEs led to rusfertide discontinuation in 10 high-risk patients (7.8%) and 10 low-risk patients (6.4%).
The frequency of TEs was similar in the rusfertide and placebo arms, irrespective of risk group during the double-blind period through week 32; among high-risk patients, 31.8% had a history of TEs prior to study entry.
The ongoing, open-label portions of the phase 3 trial are expected to provide additional information on the long-term safety and tolerability of rusfertide in patients with PV.
