Andrew Kuykendall, MD, Moffitt Cancer Center, Tampa, Florida, discusses the results of the phase 3 VERIFY trial which compared rusfertide vs placebo for patients with myeloproliferative neoplasm (MPN) polycythemia vera (PV) who required frequent phlebotomy.

The results of this analysis, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated a potential new standard of care for certain patients with myeloproliferative neoplasms, and showed that rusfertide reduced the mean number of phlebotomies and improved hematocrit control among patients treated with PV with rusfertide compared to placebo.

Transcript:

Hi, my name's Andrew Kuykendall from Moffitt Cancer Center in Tampa, Florida. I'm here at ASCO 2025 and just presented the VERIFY study, which is a phase 3 study looking at the use of rusfertide in patients with polycythemia vera.

A brief background on the study, patients with polycythemia vera are at an increased risk for cardiovascular events including thrombotic events. The primary way in which we manage that in the current treatment paradigm is we perform therapeutic phlebotomies to try to bring their hematocrit down and actually try to achieve a hematocrit of consistently less than 45%. Oftentimes, this requires us to do repeated therapeutic phlebotomies and drain patients of their blood until they're so iron deficient that they can't make enough red blood cells, and we call that a win, but ultimately it doesn't really feel like much of a win for patients and it seems like a relatively archaic method of bringing blood counts down.

In this study, we actually utilized our understanding of iron regulation and hepcidin, which is this master regulator of iron. Hepcidin is responsible for actually downregulating a protein called ferroportin, which delivers iron into the bloodstream, which then goes to the bone marrow. Polycythemia vera is a unique situation where you're overproducing red blood cells, but at the same time you have systemic iron deficiency, and so any iron you do bring in is actually shuttled right to the bone marrow at the expense of other iron requiring tissues. For that reason, we actually have patients that often struggle with vague symptoms of iron deficiency such as fatigue and brain fog and lack of attentiveness, and they can't really function in life as much.

Rusfertide really aimed to do a couple of things. We wanted to know if this would be able to control hematocrit in more consistent basis without subjecting patients to therapeutic phlebotomies. In addition, we wondered if targeting phlebotomies through this kind of understanding of iron regulation might actually improve patient's symptoms.

We designed a study that was a phase 3 study, patients who were requiring consistent therapeutic phlebotomies who had polycythemia vera were randomized 1-to-1 to go on rusfertide or placebo in addition to their ongoing current standard of care. We looked at patients over 32 weeks to assess if they were phlebotomy eligible or needed phlebotomies from week 20 to 32 where the primary endpoint was looked at.

What we saw with rusfertide is that drastically reduced patient's need for phlebotomy over that period of time compared to placebo. It also more consistently maintained hematocrit levels in our goal zone and very interestingly, actually improved patient reported symptoms including fatigue as well as other myeloproliferative neoplasm related symptoms. Importantly this showed that the ability to do that with really manageable toxicity profile, the main side effects we saw were injection site reactions, which were quite mild and some mild anemia, which would be expected given the mechanism of action.

Overall, these results really support rusfertide emerging into as a part of the new standard of care for patients with polycythemia vera.

Source:

Kuykendall A, Pemmaraju N, Pettit K, et al. Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA3.