MPN Workshop of the Carolinas 2025 | Therapeutic strategies under investigation for treating patients with myelofibrosis and anemia

Anemia has always been and continues to be somewhat of an unmet need. Now it’s important to note that momelotinib is approved now, as of two years ago, is approved as a therapy for patients with myelofibrosis and anemia. But momelotinib is a JAK inhibitor. So most of us, the way we think about it is, yes, it’s great to have a JAK inhibitor that improves anemia, but it’s not necessarily indicated for those who don’t need a JAK inhibitor in the first place. So if I had a patient who just had anemia, I would probably not go with momelotinib. Although if I had somebody who needed a JAK inhibitor based on spleen and symptoms, and also had anemia, I would absolutely go with it. So given that background, there continues to be a need for drugs that are just focused on anemia, which you could use as single agents, or you could use in combination with whatever JAK inhibitor. 

So DISC-0974 is an anti-hemojuvelin antibody. So first in class, and hemojuvelin is a positive regulator of hepcidin. So by blocking it through this antibody, you are down-regulating hepcidin, which frankly has become a familiar story now. So down-regulating hepcidin means freeing up iron or not sequestering iron, making it more available for erythropoiesis in the bone marrow. So this is another clever, elegant way of doing this, ongoing trial, we will see. Phase one has been quite promising. They’re now in phase two. They have a dose, et cetera. So that is ongoing. 

There is also a very nice trial called ODYSSEY, which is not a new drug, it’s momelotinib and luspatercept, but for the first time they are together. So momelotinib as an ACVR1 inhibitor luspatercept as a TGF super family I should say, or activin receptor ligand trap. That’s really the correct way of saying the class – it’s an activin receptor ligand trap. So for the first time putting these two together, which can act on different stages of erythropoiesis. So again, not new drugs, familiar mechanisms, but for the first time bringing them together. And we know both work. We know both work for anemia. So this is called the ODYSSEY trial. It’s for transfusion dependent patients who may or may not have been exposed to a JAK inhibitor. So they can be JAK naive or pre-treated. So that is another important trial that is ongoing. 

And then luspatercept, we will learn more in the coming days, but there were top line results recently released by BMS on their phase three trial in myelofibrosis in transfusion dependent patients who are on a stable dose of a JAK inhibitor. But that trial actually just missed its primary endpoint. Again, this is a drug we have all used off-label, widely used, we have a phase two that’s published, we know it works. But again this is interesting and unexpected news, but we will see what that might hold for the future for this for this drug.

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