Rusfertide led to thromboembolic adverse effects (TEs) in 10.0% of patients with phlebotomy-dependent polycythemia vera (PV), according to long-term follow-up data from the phase 2 REVIVE trial (NCT04057040) and phase 3 THRIVE extension study (NCT06033586) presented at the
After a median follow-up of 4.4 years, 7 of 70 patients (10.0%) enrolled in REVIVE experienced an on-study TE, and the incidence rate of TEs across both studies was 3.0 (95% CI, 0.7-5.3) per 100 patient-years. Median thrombosis-free survival (TFS) and event-free survival (EFS) were not reached in the intention-to-treat (ITT) population or in prespecified subgroups by PV risk category or prior cytoreductive therapy (CRT) status.
“Overall, these long-term data provide additional information about the occurrence of TEs and other events following rusfertide exposure that are of clinical significance in the setting of PV,” lead study author Naveen Pemmaraju, MD, of The University of Texas MD Anderson Cancer Center, and colleagues wrote in a poster presentation of the data.”
Rusfertide is a first-in-class, subcutaneously injected, self-administered peptide mimetic of the endogenous hormone hepcidin, the principal regulator of iron homeostasis. In the phase 2 REVIVE trial, rusfertide met the study's primary end point of response for hematocrit control (<45%), reduction in therapeutic phlebotomy, and completion of the treatment regimen in patients with phlebotomy-dependent PV.
REVIVE enrolled patients across a dose-finding part, a randomized withdrawal part, and an open-label extension part; patients who completed the open-label extension were eligible to continue rusfertide in the ongoing phase 3 THRIVE extension study.
This post hoc analysis included all patients enrolled in REVIVE and THRIVE, plus those who transitioned between studies. TEs and hemorrhage were defined per the FDA Office of New Drugs' Custom Medical Queries, version 4.0. TFS was defined as freedom from death or an arterial thrombotic event (eg, ischemic or hemorrhagic stroke, myocardial infarction, transient ischemic attack) or a venous thrombotic event (eg, deep vein thrombosis, pulmonary embolism, splanchnic thrombosis). EFS was defined as TFS plus freedom from grade 3 or higher hemorrhage or a post-PV progression event (eg, myelofibrosis, myelodysplastic syndrome, acute myeloid leukemia).
The data cutoff was December 10, 2025, at a median follow-up of 4.4 years.
Seventy patients enrolled in REVIVE had a median age of 58 years (range, 27-77), were mostly male (70.0%), had high-risk PV (55.7%), and received concurrent CRT (47.1%); 18.6% of this group had a history of TEs before study entry.
Forty-six of the 70 patients (65.7%) transitioned to the open-label THRIVE extension study; this subgroup had similar baseline characteristics (median age, 58 years [range, 27-77]; male, 73.9%; high-risk PV, 56.5%; concurrent CRT, 54.3%). Median duration of rusfertide exposure was 2.5 years (range, 0.06-4.1) in REVIVE overall and 4.3 years (range, 2.7-5.5) across both studies among patients who transitioned to THRIVE.
After a median follow-up of 4.4 years, 7 of 70 patients (10.0%) had an on-study TE; 6 of these events occurred during REVIVE. All 7 patients had high-risk PV and additional baseline risk factors, including hypertension, dyslipidemia, elevated white blood cell count, or vascular disease, and 5 of the 7 were receiving concurrent hydroxyurea. On-study events included ischemic stroke, mesenteric arterial occlusion with acute myocardial infarction, portal vein thrombosis, deep vein thrombosis, transient ischemic attack, pulmonary embolism, and hemorrhagic stroke. Six of the 7 patients continued rusfertide after their event, and 3 remained on treatment as of the data cutoff.
Median TFS was not reached in the ITT population, in patients with low- or high-risk PV, or when stratified by arterial vs venous event type. At 5 years, the estimated probability of remaining TE-free was 88% (95% CI, 0.78-0.94) in the ITT population.
Two of 70 patients (2.9%) had a post-PV progression event during long-term follow-up, including 1 case of myelofibrosis and 1 case of acute myeloid leukemia. Median EFS—defined as TFS plus freedom from grade 3 or higher hemorrhage or a post-PV progression event—was not reached in the ITT population or in any of the subgroups investigated by PV risk category or CRT status.
Pemmaraju N, Kuykendall AT, Gerds A, Gotlib J, Ritchie EK, Pettit K, et al. Thromboembolic and progression events in phlebotomy-dependent patients with polycythemia vera (PV): long-term results from the phase 2 REVIVE and THRIVE open-label extension studies. Presented at: 31st Congress of the European Hematology Association (EHA); June 11-14, 2026; Stockholm, Sweden. Abstract PF890.
