Dr Kremyanskaya on the Rationale for Investigating Rusfertide in Phlebotomy-Dependent PV

Marina Kremyanskaya, MD, PhD, assistant professor, medicine, hematology, and medical oncology, Icahn School of Medicine, Mount Sinai, medical director, Inpatient Oncology Unit, The Mount Sinai Hospital, discusses the rationale for investigating rusfertide (PTG-300) in the phase 2 REVIVE trial (NCT04057040) for patients with phlebotomy-dependent polycythemia vera (PV).

The standard of care for PV in patients who display uncontrolled erythrocytosis has historically been therapeutic phlebotomy, Kremyanskaya begins, adding that this is done to maintain a hematocrit level of less than 45%. Notably, if a patient is considered to have high-risk disease, they will be treated with therapeutic phlebotomy, as well as with cytoreductive therapies, she notes. In comparison, some patients who are considered low risk are treated with cytoreductive therapy if they are symptomatic or cannot undergo phlebotomies, Kremyanskaya says.

Investigators continue to develop rusfertide, a hepcidin mimetic, for the treatment of PV, Kremyanskaya expands. A hepcidin mimetic is a hormone peptide produced by the liver that controls erythrocytosis and hematologic malignancies, she says. Rusfertide was developed on the hypothesis that hepcidin can be used as a controller of erythrocytosis, which can then be considered a chemical phlebotomy or areplacement for phlebotomy in this patient population, Kremyanskaya emphasizes.

Notably, some patients with PV become iron deficient because of phlebotomies, she adds. This is important because symptoms of PV are related to iron deficiency and the inflammatory nature of the myeloproliferative neoplasm, Kremyanskaya continues. In REVIVE, when patients received rusfertide, the dose was up titrated to get them to the goal hematocrit level of less than 45%, and several patients were able to maintain that dose, Kremyanskaya says. Overall, these patients now may not need a therapeutic phlebotomy, as many reported feeling better and had improvements in their systemic symptoms following treatment, Kremyanskaya concludes.