Rusfertide Cuts Phlebotomy Need in Polycythemia Vera: Andrew Kuykendall, MD

April 10, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

With an expected completion date sometime in June, the phase 3 VERIFY trial (NCT05210790) will soon conclude its investigation of rusfertide (Takeda) as add-on therapy to a patient’s current course of treatment for their polycythemia vera. The investigative agent has already received breakthrough therapy, orphan drug, and fast track designations from the FDA.

In this fourth part of a discussion with The American Journal of Managed Care®, Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center and VERIFY investigator, speaks to the impressive patient-reported outcomes seen thus far.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

Can you summarize the key findings seen so far in the phase 3 VERIFY study?

Super exciting results that we saw. The study design, a lot of this was really built on a phase 2 study that was published in The New England Journal of Medicine that took patients with polycythemia vera who were requiring phlebotomies on a regular basis. That study basically put everyone on rusfertide and assessed over time their need for phlebotomy. There are a couple of different nuances to that study, but I would say the take home point of what we saw is that rusfertide very effectively eliminated the need for these patients that were regularly needing phlebotomies to need any phlebotomies at all—really rapidly reduced that and so certainly paved the way for designing a phase 3 clinical trial that could show that in comparison to standard therapy.

This trial took patients that had polycythemia vera that were requiring regular phlebotomy—so at least 3 over the preceding 28 weeks or 5 over the course of the prior year—and it randomized them to either stay on their standard therapy and add rusfertide or stay on their standard therapy and add a placebo. Everyone was treated in kind of the standard way, even if you were randomized to the “placebo arm”; that was just the standard therapy. If you were on cytoreductive therapy like hydroxyurea or interferon or ruxolitinib—these are agents we use to treat the disease as well—you stayed on those agents and you continued to get phlebotomies, as you would if you if you were kind of in routine clinical care. Then the other group did the same thing, but they added on rusfertide as a weekly subcutaneous injection. For 20 weeks, there was a a dose-finding period where rusfertide, the doses were increased based on hematocrit level and various different control of the disease.

The primary end point, at least in the US, was looking at the number of patients that were “phlebotomy eligible,” meaning that they needed a phlebotomy to control their disease—and that was being looked at between weeks 20 and 32. What we found is significantly more patients in the placebo group, so in the patients that were not receiving rusfertide, were “phlebotomy eligible” during that period of time. Another way to say that is, more patients in the rusfertide group did not need a phlebotomy during that that critical time period. Just another way of showing the control that rusfertide has, and that was the primary end point. Based on the phase 2 data, we certainly were optimistic that this was going to be reached.

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Rusfertide Reduces Phlebotomy Need, Improves Symptom Control in Polycythemia Vera

November 21, 2024

Author(s): Alexandra Gerlach, Associate Editor

Rusfertide (Takeda; Protagonist Therapeutics Inc) controlled erythrocytosis, maintained a hematocrit of less than 45% and reduced or eliminated the use of phlebotomy in patients with polycythemia vera (PV), according to data from the REVIVE trial (NCT04057040). Published in The New England Journal of Medicine, the results suggest the agent could become an additional therapeutic tool to reduce disease-related symptoms and the need for phlebotomy.1,2

Blood cells | Image Credit: © Ifti Digital – stock.adobe.com

PV is a rare type of blood cancer characterized by the overproduction of red blood cells in the bone marrow, contributing to blood clots, as well as the development of other blood disorders, such as myelofibrosis (MF). Both PV and MF are types of BCR‐ABL1‐negative myeloproliferative neoplasms with shared mutations and are associated with risk of thrombosis, hemorrhagic complications, and progression to acute myeloid leukemia. Approximately 1 in 4 patients with PV will develop MF, which is referred to as post–polycythemia vera myelofibrosis.3-5

Standard-of-care treatment for PV focuses on symptom reduction including treatments for to reduce itching or control blood cell counts, using agents such as hydroxyurea (Droxia; Bristol Myers Squibb) or ruxolitinib (Jakafi; Incyte Corp). The most common treatment for PV is frequent blood withdrawals to decrease blood volume, which is done via phlebotomy.5

Rusfertideis is an injectable, peptide mimetic of hepcidin. Hepcidin, produced in the liver, is a master regulator of iron trafficking. Some preclinical models suggest that increasing hepcidin could help control red blood cell production in patients with PV. In the phase 2 REVIVE trial, rusfertide demonstrated favorable safety and efficacy, with the potential to greatly decrease or eliminate the need for phlebotomy.2

The international, phase 2 REVIVE trial is divided into 2 parts. In part 1, patients were enrolled in a 28-week dose-finding assessment of rusfertide. In part 2, a double-blind, randomized withdrawal period, patients were assigned 1:1 ratio to receive either rusfertide (n = 30) or placebo (n = 29) for 12 weeks. The primary end point was response, which was defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Outcomes were reported by patients and were assessed using the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).2

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