KEY TAKEAWAYS
- The phase 2 REVIVE study aimed to investigate the effect of rusfertide (PTG-300), a hepcidin-mimetic, on therapeutic phlebotomy (TP) and patient-reported symptoms in patients with polycythemia vera (PV).
- The study found that treatment with rusfertide significantly reduced the need for therapeutic phlebotomy in patients with PV.
- Rusfertide is promising as an investigational drug for treating PV. It effectively maintained hematocrit levels, reduced the need for phlebotomy, reversed iron deficiency, and improved PV-related symptoms.
To reduce the incidence of thrombotic events, patients with polycythemia vera (PV) are treated with periodic therapeutic phlebotomy (TP) to sustain hematocrit levels of 45%. Since many patients with PV are seen irregularly, they may experience intervals with hematocrit levels >45%, which may increase thrombosis risk, particularly in patients with high TP needs. Hepcidin is the primary hormone that regulates iron homeostasis in the organism. Researchers anticipate elevated hepcidin levels will decrease iron availability and regulate excessive erythropoiesis. Researchers hypothesized that rusfertide (PTG-300), a hepcidin-mimetic, would reduce the need for erythropoiesis and phlebotomy in patients with polycythemia vera, alleviating PV-related symptoms. To investigate the effect of rusfertide on TP and patient-reported symptoms in PVMethods: PTG-300-04 is a Phase 2 trial (NCT04057040) comprised of three parts: a 28-week dose-finding; a 12-week blinded randomized withdrawal of rusfertide versus placebo (1:1); and a 52-week open-label extension. PV diagnosis (by 2016 WHO criteria) and 3 phlebotomies with or without concurrent cytoreductive therapy to sustain hematocrit 45% in the 24 weeks before enrollment are eligibility requirements. Rusfertide was administered subcutaneously weekly and was added to each subject’s pre-study treatment for PV; the dose of rusfertide was adjusted to maintain a hematocrit of 45%.
Patients filled out the MPN-SAF TSS questionnaire during protocol-mandated visits. On a scale from 0 to 10, MPN-SAF TSS items are considered “moderate” if symptoms were rated 4-6 and “severe” if symptoms were ranked 7-10. The MPN-SAF TSS ranges from 0 to 100, with each of the 10 queries having a range of 0 to 10. Higher scores indicate a more severe condition. In the first part of the study, 70 patients were enrolled; 61 completed the dose titration through 28 weeks, and 9 dropped out. The most common reason for study termination was subject disengagement. The mean number of TPs decreased from 4.7 in 28 weeks before treatment with rusfertide to 0.4 in 28 weeks of therapy with rusfertide (P=0.001). During 28 weeks of rusfertide treatment, approximately 60% of patients did not require TP, while 26% required TP. At baseline, the mean MPN-SAF TSS score was 15,6 compared to 14, 1 after 16 and 12 after 28 weeks of treatment. The average change from the initial condition was -2.2 (n = 57, P = 0.056). At Week 28, fatigue in patients with moderate baseline severity improved significantly (mean change = -1.5, P=0.006), and inactivity improved significantly (mean change = -2, P=0.003). At week 28, subjects with moderate concentration difficulties at baseline demonstrated improvement (mean change = -2, P= 0.077). The concentration of patients with high baseline severity improved (mean change = -4.2, P=0.012) at week 28 (P=0.012). The most common adverse events (AE) were injection site reactions (ISR), reported by 86% of patients and decreased in frequency over time. The majority of ISRs were grade 1 or 2 and transient. One participant dropped out of Part 1 due to an ISR. Two patients discontinued treatment due to an adverse event, one during the double-blind, randomized withdrawal and the other during the open-label extension. These clinical trial results suggest that rusfertide is a promising investigational drug for treating PV in terms of maintaining hematocrit at 45%, reversing iron deficiency, potentially eliminating the need for TP, and improving PV-related symptoms.
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04057040
Andrew Kuykendall, Marina Kremyanskaya, Yelena Ginzburg, Naveen Pemmaraju, Abdulraheem Yacoub, Frank Valone, Sarita Khanna, Suneel Gupta, Srdan Verstovsek, Ronald Hoffman/RUSFERTIDE (PTG-300) IMPROVES POLYCYTHEMIA VERA (PV) RELATED SYMPTOMS IN PV PATIENTS/Inc, M. G. (n.d.). RUSFERTIDE (PTG-300) IMPROVES POLYCYTHEMIA VERA (PV) RELATED… by Dr. Andrew Kuykendall. Library.ehaweb.org. Retrieved July 15, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/385466/andrew.kuykendall.rusfertide.28ptg-30029.improves.polycythemia.vera.28pv29.related.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D278Placebo88%2Atrend%3D4016%2Amarker%3D4178
