Imagine a future where patients with polycythemia vera (PV) no longer face the burden of frequent phlebotomies. That future might be closer than you think. New research presented at the American Society of Hematology (ASH) 2025 Annual Meeting reveals that rusfertide, a weekly self-injected peptide, could revolutionize PV management. But here's where it gets controversial: could this treatment truly replace the long-standing practice of therapeutic phlebotomy, and what does that mean for patient care?
Hematologist-oncologist Dr. Andrew Kuykendall from Moffitt Cancer Center in Tampa, Florida, shared extended data from the phase 3 VERIFY study, showing that rusfertide effectively maintained hematocrit levels and significantly reduced the need for phlebotomy over 52 weeks. Of the 147 patients who continued rusfertide past 32 weeks, 61.9% avoided phlebotomy entirely during this period. Even more striking, 77.9% of patients who switched from placebo to rusfertide at 32 weeks remained phlebotomy-free from weeks 40 to 52, compared to just 32.9% during the initial 32 weeks. Both groups maintained a mean hematocrit below 43%.
Rusfertide, a peptide mimetic of the hormone hepcidin, plays a crucial role in iron regulation. While not yet FDA-approved for PV, it has demonstrated the ability to safely control blood counts, reducing the risk of cardiovascular events that can lead to severe symptoms or death if left unchecked. Dr. Kuykendall emphasized, “This therapy not only controls hematocrit but also improves disease-related symptoms often worsened by current treatments.”
PV patients typically overproduce red blood cells, leading to symptoms like itching, night sweats, difficulty concentrating, and severe fatigue. Maintaining hematocrit below 45% is critical to reducing the risk of major cardiovascular events, a goal traditionally achieved through therapeutic phlebotomy and, occasionally, cytoreductive therapy. However, phlebotomy often exacerbates iron deficiency, ties patients to frequent healthcare visits, and can be poorly tolerated. Real-world studies also show that phlebotomy is rarely administered optimally, leaving patients at risk.
And this is the part most people miss: rusfertide could offer a more consistent and patient-friendly alternative. In the VERIFY trial, patients on rusfertide had a mean of 0.5 phlebotomies compared to 1.8 in the placebo group (P < .0001). Additionally, 62.6% of rusfertide-treated patients maintained hematocrit below 45%, versus 14.4% in the placebo group (P < .0001). The new analysis showed that from weeks 32 to 50, the median time to first phlebotomy was not reached in either group, highlighting the treatment’s durability.
Patient-reported outcomes, such as fatigue and myelofibrosis-related symptoms, also improved significantly and were sustained over time. While injection-site reactions (47.4%), anemia (25.6%), and fatigue (19.6%) were the most common side effects, they were mostly mild to moderate. Importantly, serious adverse events were rare, and non-PV malignancies remained stable, addressing concerns about potential risks.
But here’s the thought-provoking question: If rusfertide can eliminate the need for phlebotomy, how will this shift impact the overall management of PV? Dr. Kuykendall noted that it could allow for better optimization of cytoreductive therapy doses, potentially improving tolerability. However, some experts argue that phlebotomy, despite its drawbacks, remains a proven method. What do you think? Could rusfertide truly replace this long-standing practice, or is there still a place for phlebotomy in PV care?
Dr. Gabriela S. Hobbs of Harvard Medical School praised the study’s “excellent” results, highlighting the durability of responses and the absence of new safety concerns. She also noted that rusfertide is the first of several promising medications that could eliminate therapeutic phlebotomy, a significant logistical and emotional burden for PV patients.
As the VERIFY study continues and FDA approval is pursued, the potential for rusfertide to transform PV treatment is undeniable. But the debate over its role in replacing phlebotomy is just beginning. What’s your take? Share your thoughts in the comments below—let’s keep the conversation going!
