Clinical Insights: VERIFY Trial Shows Rusfertide’s Potential to Transform PV Treatment (Full Video)
Key Points
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Management of polycythemia vera (PV) centers on maintaining a hematocrit level below 45%.
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Although effective for hematocrit reduction, frequent phlebotomies can drive iron deficiency, worsen fatigue, cause fluctuating control, and increase treatment burden.
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Rusfertide, a hepcidin mimetic, addresses an unmet need in PV by reducing reliance on phlebotomy.
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The VERIFY trial, which studied rusfertide, met its primary and secondary end points, including patient-reported outcomes, with consistent benefit across subgroups.
Myeloproliferative Neoplasms: Treating Polycythemia Vera
Polycythemia vera remains a common and challenging myeloproliferative neoplasm in oncology practice, with clinicians balancing thrombotic risk reduction, symptom control, and long-term quality of life (QOL).
Standard management centers on maintaining a hematocrit below 45% with low-dose aspirin, phlebotomy, and cytoreductive therapy for high-risk patients, yet these approaches can be limited by treatment burden, iron deficiency, and persistent symptoms.
New data from the phase 3 VERIFY study, presented at the 2025 ASH Annual Meeting (ASH 2025), demonstrated that rusfertide sustained hematocrit control and response, with no new safety concerns.
At the meeting, the hosts of the Oncology Brothers podcast—Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center—led a roundtable discussion on the current treatment landscape for PV and the potential role of rusfertide in reshaping disease management. They were joined by three hematology experts: Talha Badar, MBBS, MD, of Mayo Clinic; Aaron Gerds, MD, of Cleveland Clinic; and Andrew Kuykendall, MD, of Moffitt Cancer Center.
Unmet Needs in Polycythemia Vera
Dr. Rahul Gosain began by asking why PV treatment focuses on decreasing the hematocrit in terms of cytotoxic risk or with phlebotomy. The goal in PV is to reduce thrombotic risk, according to Dr. Badar. However, achieving target levels alone is often not sufficient. Many patients continue to experience fatigue related to iron deficiency from repeated phlebotomies and microvascular symptoms—including dizziness, paresthesia, and pruritus—that may not correlate with hematologic control.
These limitations highlight the need for sustained hematocrit control and supportive care strategies that better address symptoms, improve QOL, and reduce the burden of clinic visits, Dr. Badar said.
Clinical Implications From the VERIFY Trial
Rusfertide, a potential game changer in the field, offers benefits beyond those of traditional therapies. This self-administered subcutaneous injectable peptide mimics hepcidin. The medication slows excess red blood cell production, keeps hematocrit under control, reduces the need for phlebotomies, and allows iron stores to rebuild, Dr. Kuykendall explained.
In the VERIFY trial, patients with PV who required phlebotomies, with or without cytoreductive therapy, were randomized 1:1 to rusfertide or placebo. The dose was titrated over 20 weeks, and investigators assessed the need for phlebotomies and hematocrit control from weeks 20 to 32.
Part 1b, presented at ASH 2025, showed hematocrit control in more than 70% of patients, met both primary and secondary end points, and demonstrated durable improvements in patient-reported outcomes—even among those who crossed over from placebo, Dr. Badar said.
“The beauty of the trial is its practicality—it worked regardless of cytoreductive therapy or phlebotomy use,” Dr. Gerds added. This provides advantages for patients struggling with iron deficiency, symptoms, or suboptimal control despite therapy.
When asked about clinical implications, Dr. Badar emphasized that the VERIFY regimen reduces the treatment burden, especially for older patients with PV. The average age at diagnosis is around 60 years.
Adverse Event Management
Rusfertide demonstrated a generally favorable safety profile in the VERIFY trial, which is particularly important in a chronic disease like PV that requires long-term therapy, Dr. Kuykendall said. Most patients were able to stay on treatment, including during extended phase 2 follow-up.
The most common adverse events were injection site reactions, which were mostly grade 1-2 and decreased over time. Notably, these reactions were also seen in approximately one-third of patients receiving placebo. Supportive measures, such as topical steroids and antihistamines, can help manage these reactions.
Mild anemia (25.6%) and fatigue (19.6%) were also observed during the trial.1
Most patients stabilized on 20-40 mg rusfertide weekly. Dose adjustments were primarily titration-based rather than driven by toxicity, and temporary holds were reserved for situations such as planned surgery, Dr. Kuykendall said. Importantly, continuous therapy is required, as treatment interruptions can lead to rapid hematocrit rebound, he added.
The VERIFY trial also showed improvements in PROMIS Fatigue Short Form 8a scores and Myelofibrosis Symptom Assessment Form scores.
Overall, the panelists agreed that for symptomatic patients with PV, rusfertide may improve QOL and outcomes, making it a promising addition to the treatment landscape.