Polycythemia vera (PV) is characterized by red blood cell overproduction. Rusfertide is a subcutaneous, self-injected, first-in-class peptide hepcidin mimetic that decreases erythrocytosis.

VERIFY (NCT05210790) is a global, ongoing phase 3 study designed to assess rusfertide vs placebo (PBO) in phlebotomy (PHL)-dependent patients with PV receiving standard of care (SOC) therapy.

In VERIFY Part 1a (Weeks 0–32), pts requiring frequent PHL with or without stable cytoreductive therapy (CRT) to control hematocrit (Hct) were randomized (1:1) to receive once-weekly rusfertide or PBO. Pts were stratified by concurrent PV therapy. All patients completing Part 1a were eligible for open-label rusfertide in Part 1b (Weeks 32–52). Patients who completed Part 1b were eligible to continue receiving rusfertide. The primary efficacy endpoint was the proportion of patients achieving a clinical response (i.e., absence of PHL eligibility with no PHLs from Weeks 20–32, and Part 1a completion). Key secondary endpoints (Weeks 0–32) included mean number of PHLs, proportion of patients with Hct <45%, and the mean change from baseline at end of Part 1a (Week 32) in the (1) PROMIS Fatigue Short Form 8a (SF-8a) total T-score and (2) the MFSAF v4.0 Total Symptom Score (TSS).

A total of 293 patients (male, 73.0%; median age, 57 [range, 27–86] years) were randomized to receive rusfertide (n = 147) or PBO (n = 146). In the rusfertide and PBO groups, 56.5% (n = 83) and 55.5% (n = 81) of patients, respectively, received concurrent CRT. During Weeks 20–32, significantly more patients in the rusfertide group (76.9%) achieved a clinical response vs PBO (32.9%) (p < 0.0001). The mean (standard error) number of PHLs (Weeks 0–32) was 0.5 (0.2) with rusfertide vs 1.8 (0.2) with PBO (p < 0.0001). More patients treated with rusfertide maintained Hct <45% from Weeks 0–32 vs PBO (rusfertide, 62.6%; PBO, 14.4%; p < 0.0001). For patient-reported outcomes (PROs), patients treated with rusfertide demonstrated a statistically significant improvement in the PROMIS Fatigue SF-8a total T-score and MFSAF TSS (p < 0.03). During Part 1a, the most common treatment-emergent adverse events (AEs) in the rusfertide and PBO groups, respectively, were injection site reactions (55.9% and 32.9%), anemia (15.9% and 4.1%), and fatigue (15.2% and 15.8%). Serious AEs occurred in 3.4% (rusfertide) and 4.8% (PBO) of patients; none were considered related to rusfertide. During Part 1a, new malignancies were reported in 1 (rusfertide) and 7 (PBO) patients.

In patients with PV receiving SOC therapy, rusfertide resulted in a statistically significant reduction in the mean number of PHLs and improved Hct control. Rusfertide is the first investigational agent to target the hepcidin pathway to control Hct and the first agent to prospectively demonstrate a statistically significant improvement in the PROMIS Fatigue SF-8a and MFSAF PROs in patients with PV. Rusfertide had a safety and tolerability profile consistent with rusfertide in prior studies. ©2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting. All rights reserved.