VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy

Purpose Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide is a subcutaneous, injectable, hepcidin mimetic peptide that suppresses erythrocytosis. The phase III VERIFY trial evaluated the efficacy and safety of rusfertide in phlebotomy-dependent patients with PV and poorly controlled hematocrit. Methods In VERIFY Part 1a (32 weeks), patients requiring frequent phlebotomy were randomly assigned (1:1, double-blind) to receive rusfertide or placebo with or without cytoreductive therapy. The primary efficacy end point was clinical response (absence of phlebotomy eligibility; weeks 20-32). Key secondary end points (baseline to week 32) included mean number of phlebotomies, proportion of patients who maintained hematocrit <45%, and mean change from baseline in patient-reported outcomes (Patient-Reported Outcomes Measurement Information System [PROMIS] Fatigue Short Form 8a [SF-8a] T score and Myelofibrosis Symptom Assessment Form [MFSAF] Total Symptom Score-7 items [TSS7]). Results Patients (N = 293) were randomly assigned to rusfertide (n = 147) or placebo (n = 146). Significantly more patients (n = 113, 77%) achieved a clinical response with rusfertide versus placebo (n = 48; 33%; P < .0001). Compared with placebo, rusfertide reduced mean ± standard deviation number of phlebotomies (0.5 ± 1.2 v 1.8 ± 1.5; P < .0001) and was superior in maintaining hematocrit <45% (n = 92 [63%] v n = 21 [14%]; P < .0001). Rusfertide led to a significant improvement in the PROMIS Fatigue SF-8a T-score and MFSAF TSS7 versus placebo ( P = .0252 and .0240, respectively). Injection site reactions, anemia, and fatigue were the most common adverse events. No deaths were reported. Conclusion Rusfertide significantly improved hematocrit control, reduced the need for phlebotomy, and improved patient-reported symptoms versus placebo in phlebotomy-dependent patients with PV who were also receiving standard-of-care therapy.

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Journal
Journal of Clinical Oncology
Published
2026-10-13
DOI
https://doi.org/10.1200/jco-26-00992
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
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article
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article

VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy

Yuriy Drebit, Francesca Palandri, Antonín Hluší, Steffen Koschmieder et al.
Journal of Clinical Oncology
Myeloproliferative Neoplasms: Diagnosis and Treatment
article

VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy

Yuriy Drebit, Francesca Palandri, Antonín Hluší, Steffen Koschmieder, Jean‐Jacques Kiladjian, Samah Alimam, Anna Jonášová, Aniket Bankar, Patricia Vélez Tenza, Ilya Kirgner, Daniel Sasca, Nikki Granacher, Martin H. Ellis, Giulia Benevolo, Pedro Oyuela, Fahri Şahin, Justyna Rybka, Adrian Schwarzer, Alessandro Morotti, Münci Yağcı, Valentín García‐Gutiérrez, María Laura Fox, Balázs Tajti, Fiorenza Barraco, Alessandro Maria Vannucchi, Andrew Tucker Kuykendall, David M. Ross, Thomas Illmer, Veronika Buxhofer‐Ausch, Jiřı́ Mayer, Alessandro Rambaldi, Frank H. Valone, Kristen Marie Pettit, Marcin Rymko, Marina Kremyanskaya, Pervin Topçuoğlu, Joseph Michael Scandura, Dominiek Mazure, Blanca Xicoy Cirici, Eran Zimran, Alessandro Lucchesi, Abdulraheem Yacoub, Albert Woelfler, Jacek Krzanowski, Gill Harinder Singh, Harinder Singh Gill, Naveen Pemmaraju, Timothy Devos, Daniel Lechner-Radner, Adi Shacham Abulafia, A. Villanueva Álvarez, Arturo Molina, Alessandro Maria Vannucchi, Françoise Boyer, Philipp le Coutre, Sarita Khanna, Jarosław Czyż, Tamanna Haque, Pilar Giraldo, Valerio De Stefano, Peter Tan, Elisa Rumi, Jie Xiao, Andrew Perkins, María Laura Fox, Phillip Dinh, Jean-Jacques Kiladjian, Ciro Rinaldi, Suneel Gupta, Gabriela Cesarman, Peter te Boekhorst, Alessandro Isidori, Bruce Bank, Tadeusz Robak, Richard Kaczmarski, Christopher Benton, Arpad Illes, Andrzej Mital, Thomas Wolff, Aniket Bankar, Mehmet Yilmaz, Rosa Ayala Diaz, on behalf of the VERIFY Investigators, Swarna Chanduri, Jiri Mayer, Joseph Shatzel, Juan Cattoni, Clemens Schmitt, Santiago Osorio Prendes, Oscar Eduardo Castellanos Velazco, Mauricio Chandia, Peter Westerweel, Julie Glanville, Annalisa Andreoli
article en

Abstract

Purpose Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide is a subcutaneous, injectable, hepcidin mimetic peptide that suppresses erythrocytosis. The phase III VERIFY trial evaluated the efficacy and safety of rusfertide in phlebotomy-dependent patients with PV and poorly controlled hematocrit. Methods In VERIFY Part 1a (32 weeks), patients requiring frequent phlebotomy were randomly assigned (1:1, double-blind) to receive rusfertide or placebo with or without cytoreductive therapy. The primary efficacy end point was clinical response (absence of phlebotomy eligibility; weeks 20-32). Key secondary end points (baseline to week 32) included mean number of phlebotomies, proportion of patients who maintained hematocrit <45%, and mean change from baseline in patient-reported outcomes (Patient-Reported Outcomes Measurement Information System [PROMIS] Fatigue Short Form 8a [SF-8a] T score and Myelofibrosis Symptom Assessment Form [MFSAF] Total Symptom Score-7 items [TSS7]). Results Patients (N = 293) were randomly assigned to rusfertide (n = 147) or placebo (n = 146). Significantly more patients (n = 113, 77%) achieved a clinical response with rusfertide versus placebo (n = 48; 33%; P < .0001). Compared with placebo, rusfertide reduced mean ± standard deviation number of phlebotomies (0.5 ± 1.2 v 1.8 ± 1.5; P < .0001) and was superior in maintaining hematocrit <45% (n = 92 [63%] v n = 21 [14%]; P < .0001). Rusfertide led to a significant improvement in the PROMIS Fatigue SF-8a T-score and MFSAF TSS7 versus placebo ( P = .0252 and .0240, respectively). Injection site reactions, anemia, and fatigue were the most common adverse events. No deaths were reported. Conclusion Rusfertide significantly improved hematocrit control, reduced the need for phlebotomy, and improved patient-reported symptoms versus placebo in phlebotomy-dependent patients with PV who were also receiving standard-of-care therapy.

Journal of Clinical Oncology
Royal Adelaide Hospital (AU), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Oregon Health & Science University (US), Universidad de Alcalá (ES), Johannes Gutenberg University Mainz (DE), Cornell University (US), Masaryk University (CZ), University of Michigan (US), Princess Margaret Cancer Centre (CA), Moffitt Cancer Center (US), Protagonist Therapeutics (United States) (US), The University of Kansas Cancer Center (US), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Azienda USL di Bologna (IT), Instituto Ramón y Cajal de Investigación Sanitaria (ES), Vall d'Hebron Hospital Universitari (ES), Hôpital Saint-Louis (FR), Hospital Universitario Ramón y Cajal (ES), Université Paris Diderot (FR), RWTH Aachen University (DE), University of Hong Kong (HK)
Openalex Percentile: Top 14%
Myeloproliferative Neoplasms: Diagnosis and Treatment
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