VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy

Purpose Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide is a subcutaneous, injectable, hepcidin mimetic peptide that suppresses erythrocytosis. The phase III VERIFY trial evaluated the efficacy and safety of rusfertide in phlebotomy-dependent patients with PV and poorly controlled hematocrit. Methods In VERIFY Part 1a (32 weeks), patients requiring frequent phlebotomy were randomly assigned (1:1, double-blind) to receive rusfertide or placebo with or without cytoreductive therapy. The primary efficacy end point was clinical response (absence of phlebotomy eligibility; weeks 20-32). Key secondary end points (baseline to week 32) included mean number of phlebotomies, proportion of patients who maintained hematocrit <45%, and mean change from baseline in patient-reported outcomes (Patient-Reported Outcomes Measurement Information System [PROMIS] Fatigue Short Form 8a [SF-8a] T score and Myelofibrosis Symptom Assessment Form [MFSAF] Total Symptom Score-7 items [TSS7]). Results Patients (N = 293) were randomly assigned to rusfertide (n = 147) or placebo (n = 146). Significantly more patients (n = 113, 77%) achieved a clinical response with rusfertide versus placebo (n = 48; 33%; P < .0001). Compared with placebo, rusfertide reduced mean ± standard deviation number of phlebotomies (0.5 ± 1.2 v 1.8 ± 1.5; P < .0001) and was superior in maintaining hematocrit <45% (n = 92 [63%] v n = 21 [14%]; P < .0001). Rusfertide led to a significant improvement in the PROMIS Fatigue SF-8a T-score and MFSAF TSS7 versus placebo ( P = .0252 and .0240, respectively). Injection site reactions, anemia, and fatigue were the most common adverse events. No deaths were reported. Conclusion Rusfertide significantly improved hematocrit control, reduced the need for phlebotomy, and improved patient-reported symptoms versus placebo in phlebotomy-dependent patients with PV who were also receiving standard-of-care therapy.