Rusfertide Treatment Strengthens Response and Decreases Erythrocytosis Among Patients With Polycythemia Vera

Findings from the International Phase 2 REVIVE Trial

According to findings from the international phase 2 REVIVE trial published in The New England Journal of Medicine, treatment with rusfertide, a peptide mimetic of the master iron regulatory hormone hepcidin, strengthened responses and decreased erythrocytosis among patients with polycythemia vera (PV). Patients who received rusfertide demonstrated a mean hematocrit of less than 45% during the dose-finding period. 

Marina Kremyanskaya, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, New York, and coauthors stated, “Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis,” or a high concentration of red blood cells in the blood. “The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown,” they added. 

To expand on the available research, the study authors aimed to assess the efficacy of rusfertide among patients with polycythemia vera. The primary end point was a response, which was characterized by the hematocrit control, absence of phlebotomy, and finishing the trial regimen during part 2. The modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary was utilized to assess patient-reported outcomes of symptoms. 

A total of 70 patients with polycythemia vera were enrolled in part 1 of this trial, which was a 28-week dose-finding assessment of rusfertide. In part 2, which was a double-blind, randomized withdrawal period, 59 of these patients were assigned 1 to 1 to receive either rusfertide (n = 30) or placebo (n = 29). Results indicated that the estimated mean number of phlebotomies per year was 8.7±2.9 in the first 28-week period before the first dose of rusfertide, and 0.6±1.0 during part 1. This indicated an estimated difference of 8.1 phlebotomies per year. The mean maximum hematocrit was 44.5±2.2% during part 1, versus 50.0±5.8% within the 28 weeks before the first dose of rusfertide. 

In part 2, 60% of patients who received rusfertide experienced a response, compared to 17% of patients who received the placebo. The study authors noted that, between baseline and the end of part 1, patients with moderate or severe symptoms at baseline who received rusfertide reported a decrease in individual symptom scores on the MPN-SAF. During both parts 1 and 2, 13% of patients experienced grade 3 adverse events. No patients experienced grade 4 or 5 events. Grade 1 or 2 injection site reactions were common. 

Kremyanskaya et al concluded, “In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo.” 

Source: 

Kremyanskaya M, Kuykendall AT, Pemmaraju N, et al. Rusfertide, a hepcidin mimetic, for control of erythrocytosis in polycythemia vera. N Engl J Med. Published online: February 22, 2024. doi: 10.1056/NEJMoa2308809