Dr Kuykendall on the Rationale for Targeting the Hepcidin Pathway With Rusfertide in Polycythemia Vera

“We looked at [rusfertide in polycythemia vera] in the phase 2 REVIVE trial, [which] led to the phase 3 VERIFY study, and what we saw is that rusfertide has the ability to control hemoglobin and hematocrit, and reduce the need for phlebotomies in patients with polycythemia vera.”

Andrew Kuykendall, MD, an assistant member in the Department of Malignant Hematology at the Moffitt Cancer Center, discussed the rationale for targeting the hepcidin pathway with rusfertide (PTG-300) in patients with polycythemia vera (PV).

PV is caused by the overproduction of red blood cells, which is driven by JAK2 mutations, Kuykendall began. He noted that patients with PV are at higher risk of experiencing cardiovascular events and symptoms associated with iron deficiency, ultimately affecting patients’ quality of life. To control the overproduction of red blood cells (RBC), therapeutic phlebotomies are necessary, which drain patients of their iron to induce iron deficiency, he explained. Although this process is effective in lowering RBC counts, patients often experience poorer quality of life without iron, he added.

In the phase 3 VERIFY trial (NCT05210790), rusfertide was evaluated as a hepcidin mimetic, which is notable because hepcidin plays a key role in regulating iron homeostasis in the body, Kuykendall asserted. Furthermore, rusfertide mimics hepcidin and can withhold iron from the bone marrow, thereby controlling hematocrit without patients becoming more iron deficient, he emphasized. Of note, rusfertide was evaluated in the phase 2 REVIVE trial (NCT04057040), findings from which supported the initiation of VERIFY, he continued. The latter trial demonstrated that rusfertide could control hemoglobin and hematocrit, while reducing the necessity for phlebotomies in patients with PV, he explained. Notably, more patients had improved quality of life and symptoms with rusfertide, according to patient-reported outcomes that measured fatigue and other symptoms associated with myeloproliferative neoplasms, he reported. The VERIFY study demonstrated that rusfertide could potentially be added to the standard of care in the PV treatment paradigm, Kuykendall concluded.