Among patients with phlebotomy-dependent polycythemia vera (PV), treatment with rusfertide, a hepcidin mimetic administered weekly as a subcutaneous injection, continues to be effective, results in sustained hematocrit control, and eliminates the need for repeated phlebotomies. These results from the ongoing phase II REVIVE trial were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
Current therapies for PV include phlebotomy with and without cytoreductive therapies such as hydroxyurea, interferon, or ruxolitinib, although these are not consistently effective or tolerable for all patients. Additionally, disease symptoms may be exacerbated by phlebotomy-related iron deficiency.
“Rusfertide [allows for] tight control of hematocrit levels because the drug alters the trafficking of iron to erythroid precursor cells, therefore suppressing erythropoiesis and blocking the release of iron from tissue macrophages, which potentially alleviates the severity of systemic symptoms that have been attributed to chronic iron sufficiency,” said first author Ronald Hoffman, MD, of the Icahn School of Medicine at Mount Sinai in New York, who presented the results. “This advance is indicative of the critical role that iron metabolism plays in the pathobiology of PV, which has not been previously appreciated.”
Enrolled patients with PV were at either low or high risk of thrombotic events and required frequent phlebotomies to maintain hematocrit levels below 45%. To participate, patients were required to have had three or more phlebotomies within six months of trial enrollment. Patients received rusfertide for 28 weeks, after which they could continue therapy in the open-label extension phase for up to 36 months after a 12-week withdrawal phase.
Of 70 patients, 84% did not require a phlebotomy, 14% required one, and 2% required two during the initial 28 weeks of rusfertide treatment. The therapy was equally effective in controlling hematocrit levels in patients who were treated previously with phlebotomy alone or those who required myelosuppressive agents. Patients had been treated for up to 1.5 years and essentially did not need phlebotomies.
Patients had normalized iron stores, as measured by ferritin levels, and reduced red blood cell counts, yet therapy did not affect white blood cell or platelet counts.
Most adverse events (AEs) were grade 1 or 2. Injection site reactions were the most common, occurring with 33% of injections. There were no grade 3 AEs related to rusfertide. One grade 4 event occurred in a patient with asymptomatic thrombocytosis possibly related to rusfertide. Two patients withdrew from the trial as a result of AEs possibly related to the therapy.
“Rusfertide can potentially be used to treat virtually all patients with PV,” Dr. Hoffman said. “This drug will likely allow one to reduce the doses of myelosuppressive agents and eliminate the need for supplemental phlebotomy in order to maintain [normal] hematocrit levels associated with a reduced risk of thrombotic events.”
A phase III clinical trial in patients with PV (VERIFY) has been developed to validate these phase II results.
Any conflicts of interest declared by the authors can be found in the original abstract.
Hoffman R, Ginzburg Y, Kremyanskaya M, et al. Rusfertide (PTG-300) treatment in phlebotomy-dependent polycythemia vera. Abstract 7003. Presented at the American Society of Clinical Oncology Annual Meeting; Chicago, Illinois.