VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy.
Key claim: In phlebotomy-dependent polycythemia vera on standard-of-care therapy, rusfertide versus placebo markedly improved hematocrit control, cut phlebotomy need, and improved fatigue and total symptom scores.
Abstract
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%;< .0001). Compared with placebo, rusfertide reduced mean ± standard deviation number of phlebotomies (0.5 ± 1.21.8 ± 1.5;< .0001) and was superior in maintaining hematocrit <45% (n = 92 [63%]n = 21 [14%];< .0001). Rusfertide led to a significant improvement in the PROMIS Fatigue SF-8a T-score and MFSAF TSS7 versus placebo (= .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.
Why this matters
In phlebotomy-dependent polycythemia vera on standard-of-care therapy, rusfertide versus placebo markedly improved hematocrit control, cut phlebotomy need, and improved fatigue and total symptom scores.