Rusfertide Helps Patients With Polycythemia Vera Avoid Phlebotomy

Patients with polycythemia vera (PV) who received rusfertide were able to avoid therapeutic phlebotomy for seven months, even among those with high-risk disease, according to results from a phase II trial. Lead author Marina Kremyanskaya, MD, PhD, from the Icahn School of Medicine at Mount Sinai in New York, shared these findings at EHA2021 Virtual.

Patients with PV are typically treated with periodic therapeutic phlebotomy to maintain hematocrit levels <45% and reduce the incidence of thrombotic events. However, Dr. Kremyanskaya and coauthors explained that patients likely spend significant time between therapeutic phlebotomy with hematocrit levels >45%, and therefore at an increased risk for thrombosis. Rusfertide (formerly known as PTG-300) is a hepcidin-mimetic that helps reduce iron availability and decrease erythropoiesis in patients with PV.

In this study, researchers evaluated the effects of rusfertide on the iron status and phlebotomy requirements among patients with PV and substantial requirement for therapeutic phlebotomy.

The PTG-300-04 trial consisted of three parts: a 28-week dose-finding phase; a 12-week blinded placebo-controlled randomized withdrawal phase; and a 52-week open-label extension phase. Eligible participants had PV and had undergone at least three phlebotomies with or without concurrent cytoreductive therapy to maintain hematocrit <45% in the 24 weeks prior to enrollment.

Patients received rusfertide at doses of 10, 20, 40, 60, and 80 mg weekly, in addition to their pre-study treatment for PV. The dose of rusfertide was adjusted to maintain hematocrit <45%.

Dr. Kremyanskaya presented results from 35 patients enrolled to date, 16 of whom had low-risk PV. Prior to enrollment, patients had received between three and nine phlebotomies, with a median time of 36 days between procedures. Patients were receiving the following concurrent medications: hydroxyurea (n=8), interferon (n=3), and ruxolitinib (n=1).

Compared with the rate of therapeutic phlebotomy before rusfertide initiation, the rate after rusfertide treatment was significantly lower, the authors reported. Four patients required one phlebotomy early in the dose-finding period (within 12 weeks), three of whom have been phlebotomy-free after increasing their dose of rusfertide.

A total of 13 patients have completed 28 weeks of dosing in the first phase of the study. Of these, 10 have remained phlebotomy-free for 28 weeks. Of the remaining three patients, two required one phlebotomy each and one required two phlebotomies. This was still significantly lower than their pre-rusfertide rate, the authors noted. Overall, hematocrit was <45% at study entry and remained continuously <45% during the study.

Rusfertide also led to improvements in mean serum ferritin levels and increases in both mean corpuscular volume and mean corpuscular hemoglobin levels, “suggesting a redistribution of iron within erythropoiesis,” the researchers reported.

Regarding safety, the most frequent adverse events were injection site reactions (n=9), most of which were grade 1.

“Rusfertide looks very promising in maintaining hematocrit <45% and in eliminating the therapeutic phlebotomies in both low and high-risk PV patients,” the authors concluded. They added that these findings are limited by the small number of patients in the study and that rusfertide’s effects on PV-related symptoms is being evaluated.

Study authors report relationships with Protagonist Therapeutics, which sponsored this trial.


Kremyanskaya M, Ginzburg Y, Kuykendall A, et al. Rusfertide (PTG-300) eliminates the need for therapeutic phlebotomy in both low and high-risk polycythemia vera (PV) patients. Abstract #S200. Presented at the EHA2021 Virtual Congress, June 9-17, 2021.