Expanding on a New Way to Manage Polycythemia Vera Without Iron Deficiency

The VERIFY trial explores rusfertide’s role in managing polycythemia vera by controlling red blood cell production without causing iron deficiency symptoms, explained by Dr. Aarron Gerds from the Cleveland Clinic. Traditional treatment with phlebotomies reduces red cells by inducing iron deficiency, which leads to fatigue and other symptoms.

Rusfertide works by trapping iron, thereby tricking the bone marrow into reducing red cell production while avoiding typical iron deficiency side effects. Dr. Gerds highlights this as a novel approach in polycythemia vera treatment and contrasts it with related myelofibrosis therapy, where hepcidin levels are lowered to treat anemia.

Dr. Aaron Gerds is an assistant professor of medicine at Cleveland Clinic Taussig Cancer Institute specializing in myeloproliferative neoplasms, myelodysplastic syndromes and stem cell transplantation.

Transcript:

What do we currently know about how rusfertide affects patient symptoms? is there any evidence it improves overall quality of life compared with standard phlebotomy?

The way we typically treat polycythemia is with phlebotomies, which lead to iron deficiency — and that’s how they control red blood cell production. But iron deficiency itself can cause a lot of symptoms: fatigue, muscle and joint aches, and even pica, a craving to eat ice or dirt. Many of the symptoms patients experience are tied to iron deficiency, which is part of how phlebotomies work to treat polycythemia vera.

Rusfertide works differently. It’s a synthetic version of hepcidin, the body’s natural regulator of iron. Think of hepcidin like a cork in a bottle: your body stores iron in that bottle, and hepcidin keeps the cork in place so the iron can’t get out. When rusfertide is present, iron stays trapped in those stores, and the bone marrow is tricked into thinking the body is iron deficient, even though it’s not. That way, you can control red blood cell production without causing the typical symptoms of iron deficiency. It’s a clever approach.

We’ve known about hepcidin for a long time — it’s something we learned about in medical school — but this is really the first time we’re harnessing it in this way to treat polycythemia vera.

Here’s an even cooler part: we’re using this same pathway in the opposite direction for myelofibrosis, a closely related disease. In myelofibrosis, we often see anemia, so we’re trying to lower hepcidin levels to help boost red cell production. In polycythemia vera, we’re effectively raising hepcidin to lower red cells, and in myelofibrosis, we’re lowering hepcidin to increase them. In the same field, we’re manipulating the same pathway in two different ways to treat two different problems.

Transcript has been edited for clarity and conciseness.

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