Treatment with the investigational injectable hepcidin mimetic rusfertide effectively controlled levels of hematocrit and significantly reduced the need for phlebotomy in patients with polycythemia vera (PV). The results of this phase II trial were presented during the 2021 ASH Annual Meeting by Ronald Hoffman, MD.
The trial enrolled 63 patients with PV who had received three or more phlebotomies with or without concurrent cytoreductive treatment to maintain hematocrit below 45% in the 24 weeks before enrollment. Patients self-administered rusfertide at doses of 10 mg to 120 mg. The authors noted that doses were adjusted to maintain hematocrit below 45% during the study period, given that hematocrit levels above 45% may be associated with an increased risk of thrombosis.
The most common prior treatment received by patients was therapeutic phlebotomy monotherapy (n = 30). In the 28 weeks prior to enrollment, the median number of therapeutic phlebotomies ranged between four and 10. A total of seven patients dropped out of the study, including one who withdrew because of asymptomatic thrombocytosis.
The investigators reported that the need for therapeutic phlebotomies was “essentially eliminated” in all subgroups of patients following the start of rusfertide therapy. Hematocrit levels were maintained consistently below 45%. Additionally, there was a noticeable reduction in red blood cell (RBC) counts, as well as an increase in both mean corpuscular volume and mean corpuscular hemoglobin values following rusfertide treatment. The researchers noted that before treatment, the RBC counts and mean corpuscular volume “were consistent with systemic iron deficiency,” as often reported in patients with PV.
Patients treated with rusfertide experienced progressively elevated levels of serum ferritin that approached the normal range, suggesting systemic iron deficiency was reversed or progressing to reversal in these patients.
Approximately one-third of patients experienced a reduction of 40% or more in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Scores from baseline to week 28. Following 8 weeks of therapy, 69% of patients showed improvement from baseline on the Patient Global Impression of Change.
During the short follow-up, there were no significant increases in the frequency of the JAK2 V617F variant allele, and no thrombotic events were reported in any treated patients with PV. Injection site reactions were the most frequently reported adverse events (AEs), all of which were transient and managed by antihistamines. Most of the AEs were grade 1 to 2 in severity, and no drug-related serious AEs or grade 3 or 4 adverse reactions were reported.