Patients with polycythemia vera (PV) endure a grueling regimen of blood tests, frequent phlebotomies, and unrelenting symptoms, yet the condition presents a striking contradiction: iron deficiency coexists with an overabundance of red blood cells. Andrew Kuykendall, MD, an associate member of the Department of Hematology at Moffitt Cancer Center and principal investigator of the VERIFY trial (NCT05210790), explains that rusfertide, a synthetic hepcidin analog, disrupts this imbalance by interrupting the link between iron availability and erythrocytosis. The drug targets the core dysfunction driving PV—a cycle where excessive red cell production depletes iron stores despite deficiency.
PV is characterized by uncontrolled red blood cell proliferation, but other blood components often overproduce as well. This overproduction raises clot risk and necessitates regular phlebotomies to reduce blood counts. The paradox intensifies because patients frequently exhibit iron deficiency, yet their bodies continue to generate surplus red cells. Since iron is critical for erythropoiesis, the disease’s relentless production accelerates depletion, exacerbating fatigue, cognitive impairment, and concentration difficulties. The physical toll extends beyond symptoms: patients face repeated healthcare visits for monitoring and phlebotomies, procedures that further deplete energy and disrupt fluid balance.
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Current treatment relies on reactive blood removal after overproduction occurs, rather than addressing the underlying metabolic dysfunction. Rusfertide alters this dynamic by mimicking hepcidin, a hormone that regulates iron release from storage. Normally, when iron levels decline, hepcidin production decreases, freeing iron for red blood cell synthesis. In PV, however, hepcidin levels remain abnormally low even during deficiency, perpetuating the cycle of overproduction and depletion. By increasing hepcidin activity, rusfertide restricts iron access to the bone marrow, thereby limiting red blood cell formation.
