The current standard of care for patients with polycythemia vera (PV) is therapeutic phlebotomy (TP) alone or in conjunction with cytoreductive therapy (CRT). However, at the 66th American Society of Hematology Annual Meeting and Exposition, Aaron Gerds, MD, of Cleveland Clinic Taussig Cancer Institute in Cleveland, Ohio, presented the final results of the phase II REVIVE study showing the efficacy of rusfertide, a hepcidin mimetic, to durably control hematocrit and decrease or eliminate the need for TP in phlebotomy-dependent patients with PV treated with or without CRT.
Part one of the REVIVE study (weeks 1-28) included 70 patients who received subcutaneous rusfertide titrated to achieve hematocrit of greater than 45%. Part two (weeks 29-41) included 59 patients blindly randomized to receive rusfertide or placebo until phlebotomy or 12 weeks, whichever came first. Part three (weeks 42-197) included 58 patients enrolled in the ongoing phase II open label extension (OLE) study in which all patients received rusfertide and dose adjustments of CRT.
The primary endpoint was response defined as not meeting any phlebotomy eligibility criteria. During part two, more patients randomized to rusfertide than placebo met the primary endpoint (69.2% vs. 14.8%; p<0.0001). Moreover, patients receiving rusfertide maintained hematocrit of greater than 45% at three years.
Estimated average phlebotomy rate (EAPR) decreased from 8.5 per year prior to enrollment to less than 1.0 per year in patients on rusfertide. Those randomized to placebo experienced an increase in EAPR to 6.6 per year but returned to less than 1.0 per year upon resuming rusfertide in the OLE study. Overall, patients who remained on rusfertide maintained an EAPR of less than 1.0 per year.
Rusfertide returned participants serum ferritin levels to normal, increased mean transferrin saturation, increased serum iron levels, and slightly increased corpuscular volume. Moreover, researchers observed patients’ symptoms improved in all domains as measured by the myeloproliferative neoplasm symptom assessment form. “That can translate into an improvement in quality of life,” Dr. Gerds told ASH Clinical News.
Regarding safety, the most common treatment-emergent adverse event (TEAE) was injection site reaction in 85.7% of patients. Grade 3 TEAEs were observed in 25.7% of patients, and there were no grade 4 or 5 TEAEs. Five patients with high-risk PV experienced six thrombotic events: one venous and five arterial. Malignancies, most of which were skin cancers, were reported in 11 patients, all of whom had risk factors that may have contributed to the development of these malignancies.
“The rate of thrombosis is expected in this population based on historical data,” Dr. Gerds said. “Due to things like hydroxyurea exposure, this population is at higher risk for skin tumors, pre-cancer, skin lesions, and non-melanoma skin cancers.”
Dr. Gerds cited the design of the phase II trial as a limitation. He underscored the importance of determining the "additional benefits of controlling hematocrit ... to provide further foundation for moving rusfertide through approval and making it widely available for patients with PV.”
Researchers will confirm the efficacy of rusfertide to reduce thrombosis risk or the need for phlebotomies with or without CRT in patients with PV in the ongoing, prospective, randomized, phase III VERIFY study.
“Rusfertide offers the promise of both making people live longer and making people live better. In the near future, rusfertide could provide another option for patients with PV, not just high-risk patients but even low-risk patients who are not optimized on phlebotomies or CRT,” Dr. Gerds said. “Stay tuned.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Gerds AT, Kuykendall AT, Kremyanskaya M, et al. Final results from the phase 2 Revive study investigating the hepcidin mimetic rusfertide in patients with polycythemia vera (PV). Abstract 4559. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 9, 2024; San Diego, California.
