• Marina Kremyanskaya, Andrew T Kuykendall, Naveen Pemmaraju, Ellen K Ritchie, Jason Gotlib, Aaron Gerds, Jeanne Palmer, Kristen Pettit, Uttam K Nath, Abdulraheem Yacoub, Arturo Molina, Samuel R Saks, Nishit B Modi, Frank H Valone, Sarita Khanna, Suneel Gupta, Srdan Verstovsek, Yelena Z Ginzburg, Ronald Hoffman, and REVIVE Trial Investigators.
• From the Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai (M.K., Y.Z.G., R.H.), and the Division of Hematology and Medical Oncology, Weill Cornell Medical College (E.K.R.) - both in New York; the Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL (A.T.K.); the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (N.P., S.V.); the Division of Hematology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford (J.G.), and Clinical Research and Development, Protagonist Therapeutics, Newark (A.M., S.R.S, N.B.M., F.H.V., S.K., S.G.) - both in California; the Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland (A.G.); the Mayo Clinic, Phoenix, AZ (J.P.); the Rogel Cancer Center, University of Michigan Health, Ann Arbor (K.P.); All India Institute of Medical Sciences, Rishikesh, India (U.K.N.); and the University of Kansas Cancer Center, Westwood (A.Y.).
• N. Engl. J. Med. 2024 Feb 22; 390 (8): 723735723-735.

BackgroundPolycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.MethodsIn part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).ResultsSeventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.ConclusionsIn 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. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).Copyright © 2024 Massachusetts Medical Society.

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