Rusfertide Offers Sustainable PV Management Strategy: Andrew Kuykendall, MD

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The phase 3 VERIFY trial (NCT05210790) evaluated rusfertide, a hepcidin mimetic peptide, as a treatment for polycythemia vera (PV), a chronic leukemia and myeloproliferative neoplasm, driven by JAK2 mutations that cause overproduction of blood cells.^1,2 Current treatment focuses on reducing thrombotic risk by maintaining hematocrit (red blood cell percentage) below 45%, often through therapeutic phlebotomy—a method that is considered archaic by some and that causes iron deficiency and fails to sustain stable blood counts.

Rusfertide mimics hepcidin, a hormone regulating iron homeostasis. In PV, iron deficiency leads to low hepcidin levels, fueling excessive red blood cell production. By mimicking high hepcidin, rusfertide restricts iron availability to the bone marrow, thereby reducing red blood cell overproduction and eliminating the need for frequent phlebotomies.

VERIFY built on phase 2 results—from the REVIVE trial (NCT04057040)—randomizing PV patients requiring phlebotomies to receive either rusfertide or placebo alongside standard therapy. The primary end point was the absence of phlebotomy eligibility between weeks 20 and 32, with secondary end points assessing hematocrit control and symptom improvement (eg, fatigue).

Results showed rusfertide effectively reduced phlebotomy dependence, offering a more sustainable way to maintain hematocrit below 45%. Additionally, it allowed patients to lower doses of cytoreductive therapies (eg, hydroxyurea), minimizing adverse effects. Although not replacing cytoreductive drugs entirely, rusfertide provides an add-on therapy to optimize treatment, particularly for patients struggling with phlebotomy burdens.

Future studies may explore whether rusfertide can replace other therapies in certain patients, but VERIFY confirmed its role in improving hematocrit control and quality of life, marking a significant advancement in PV management.

At the recent American Society of Clinical Oncology annual meeting, Andrew T. Kuykendall, MD, lead investigator for VERIFY and associate member, Department of Hematology, Moffitt Cancer Center, presented top-line data from VERIFY, noting their “unprecedented” status.³

In this interview with The American Journal of Managed Care^®, he explains the goals of VERIFY and why its data on rusfertide could have paradigm-changing implications for patients who currently rely on frequent phlebotomies for relief. He also addresses the potential influences of these findings on other cytoreductive therapies while leaving the door open for future analysis of rusfertide as a treatment alternative.

References

1. A phase 3 study of rusfertide in patients with polycythemia vera (VERIFY). ClinicalTrials.gov. Updated July 17, 2024. Accessed June 10, 2025. https://clinicaltrials.gov/study/NCT05210790

2. Kuykendall AT, Pemmaraju N, Pettit KM, et al. Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV). J Clin Oncol. 2025;43(suppl 17):Abstract LBA3. doi:10.1200/JCO.2025.43.17_suppl.LBA3

3. Caffrey M. In VERIFY, rusfertide spares most patients With PV a phlebotomy for 32 weeks, improves QOL. AJMC^®. June 3, 2025. Accessed June 10, 2025. https://www.ajmc.com/view/in-verify-rusfertide-spares-most-patients-with-pv-a-phlebotomy-for-32-weeks-improves-qol