Multicenter phase 2 trial of rusfertide for control of erythrocytosis in patients with polycythemia vera

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide is an injectable hepcidin mimetic that restricts the availability of iron for erythropoiesis. The multicenter phase 2 REVIVE trial evaluated safety and efficacy of rusfertide in patients with phlebotomy-dependent PV. In the 28 weeks before the first rusfertide dose, the mean number of phlebotomies per year was 8.7 ± 2.9 and the mean maximum hematocrit was 50.0 ± 5.8%. During the 28-week rusfertide dose-finding period the mean number of phlebotomies per year was 0.6 ± 1.0 and the mean maximum hematocrit was 44.5 ± 2.2%. During the 12-week randomized withdrawal phase, a response (defined by hematocrit control, absence of phebobomy, and completion of the trial regimen) was seen in 60% of patients randomized to rusfertide and 17% of patients randomized to placebo (p=0.002). Rusfertide was associated with improvement of symptoms among patients with baseline moderate or severe symptoms. Grade 3 adverse events were seen in 13% of patients; there were no grade 4 or 5 AEs. Injection-site reactions of grade 1 or 2 in severity were common. (quick take video summary).