Mechanism and Benefits of Rusfertide in Polycythemia Vera

Aniket Bankar, MD, Princess Margaret Cancer Center in Toronto, Canada, discusses why rusfertide is considered a promising therapeutic approach for patients with polycythemia vera.

In patients with polycythemia vera, research has shown that hepcidin levels are typically low. This deficiency leads to the continuous export of iron from the body’s iron stores, which in turn contributes to uncontrolled erythropoiesis. This excessive red blood cell production is primarily driven by the JAK2 V617F mutation. The dysregulation of iron homeostasis exacerbates the condition, making it essential to find effective treatments that address this underlying mechanism.

In response to this clinical challenge, a phase 2 randomized study known as REVIVE (NCT04057040) was conducted to evaluate the efficacy of rusfertide in patients with polycythemia vera who required frequent phlebotomies, either alone or with cytoreductive treatment. The results of this phase 2 study were promising, demonstrating that approximately 60% of patients treated with rusfertide became phlebotomy-independent, significantly reducing the need for this invasive procedure.

To further confirm these encouraging results, Bankar explains that a global phase 3, placebo-controlled, randomized trial is currently underway. This study aims to validate the findings from the phase 2 trial and solidify rusfertide's position as a novel therapeutic option for patients with polycythemia vera.

Transcription:

0:09 | Rusfertide is a hepcidin mimetic therapeutic peptide. The way it works is it blocks ferroportin, the channel that exports iron from its stores. A study had shown that in patients with PV, the hepcidin levels are low, leading to continuous export of iron from the iron stores to enable uncontrolled erythropoiesis, which is being driven primarily by the JAK2 V617F mutation.

0:46 | Based on this preclinical data, the phase 2 randomized study was conducted in patients with PV who required phlebotomies with or without cytoreductive treatment. In that phase 2 study, the investigators saw that about 60% of patients became phlebotomy-independent. To confirm the results from the phase 2 study, we are now conducting a global, phase 3, placebo-controlled, randomized trial.