Rusfertide for the treatment of polycythemia vera

The US Food and Drug Administration recently approved rusfertide, a hepcidin mimetic, for the treatment of patients with polycythemia vera (PV) whose disease is inadequately controlled with available therapies.

Hepcidin is a liver-produced hormone that regulates systemic iron availability. By restricting iron supply to erythroid progenitor cells in PV, hepcidin reduces red blood cell production and erythrocytosis. In the double-blind, placebo-controlled, phase 3 VERIFY study, clinical response during weeks 20-32 was achieved by 76.9% of patients receiving rusfertide compared with 32.9% receiving placebo, with marked reductions in phlebotomy requirements. Rusfertide is administered weekly with subcutaneous injections, with dose titration from 20 mg, to maintain hematocrit levels below 45%. The most common adverse events were injection-site reactions, anemia, and fatigue. A targeted literature search was conducted in PubMed/MEDLINE through October 2026, supplemented by ClinicalTrials.gov, regulatory documents, and abstracts from major hematology meetings.

Rusfertide is the first of a novel class of agents targeting the hepcidin regulatory axis. Following its approval, it may become part of the therapeutic armamentarium for selected patients. Future studies are needed to confirm its efficacy and to further characterize its safety and its potential impact on thrombosis, clonal evolution, and disease progression.