Reducing Therapeutic Phlebotomy in Polycythemia Vera

Treatment for polycythemia vera is based on phlebotomy and induction of iron deficiency to maintain hematocrit <45% and aspirin to reduce risk for thromboembolic events; many patients supplement with cytoreductive hydroxyurea, JAK2 inhibitors, or interferon alfa. In an industry-funded phase 2 trial with a novel design, investigators tested the efficacy and safety of rusfertide, a peptide mimetic of endogenous hepcidin that induces functional iron deficiency and decreases erythropoiesis.

In part 1 of the study, 70 patients with phlebotomy-dependent disease received a 28-week dose-finding course of weekly subcutaneous rusfertide administered at 10 to 120 mg, dosed to maintain hematocrit <45%. During part 2, 59 patients were randomized to a 12-week double-blind course of continued rusfertide or placebo. In the ongoing part 3, all patients are receiving rusfertide up to year 3. Patients could continue prior cytoreductive treatment during the study.

The mean baseline phlebotomy rate was 8.7 per year, which decreased to 0.6 per year during part 1 of the study. In part 2, an ongoing response (the primary endpoint) occurred in 60% of patients randomized to rusfertide versus 17% randomized to placebo (P=0.002). Serum ferritin levels increased while patients were on rusfertide. Patient-reported symptoms improved with rusfertide treatment; 10 grade-3 adverse events occurred, and 4 patients discontinued treatment.