The 2022 Tandem Meetings | Momelotinib: a promising drug for patients with myelofibrosis

This is really something that is different than any other JAK inhibitor so far. It is a JAK inhibitor, but it also inhibits another target in the body of the person, particularly on the surface of the liver, which is a ALK2. This is a receptor that is important for the regulation of hepcidin, a protein that is the master iron metabolism protein. And in that sense that the higher the hepcidin, the lower the survival, the patients, the lower the anemia, the anemia is worse. And it seems that modifying the hepcidin, lowering, it would allow more iron availability for a terminal maturation of the erythrocytes. The anemia improves by decreasing of hepcidin. And you do this by inhibiting a ALK2. And so alternative mechanism action, not only the JAK1 and JAK2 inhibition, which is anti-proliferative and anti-inflammatory, so people feel better have a smaller spleen, but through ALK2 inhibition lowering the hepcidin meaning more iron availability for making red blood cells also improvement in anemia, particularly improvement in what we usually worry about, transfusion requirements, elimination of the transfusion requirements, people become transfusion independent, which is easy to understand anemia benefit.

Now, why are you asking me about is because I think that’s a very good reason. There was a phase III randomized study done in people who were previously treated with ruxolitinib or other JAK inhibitors in the frontline setting and stop it and were anemic. And they didn’t feel well. And may or may not have a big spleen in that setting in a blinded randomized study, momelotinib was compared to danazol, which is an anabolic steroid, which we typically give patients for anemia and when they don’t feel well.

And the publicly available results were made about six weeks ago, saying that in that blinded randomized study in a secondary setting momelotinib was very good, superior to danazol in controlling the symptoms, also the spleen, and there were benefits on the anemia, particularly, again, this is easy to understand, and I’m very happy about that making people transfusion independent, and we expect that would possibly lead to approval momelotinib next year. And then you’re going to have a number four JAK inhibitor on the market in the United States, at least for therapy of myelofibrosis patients, but this one would be in my view, possibly the number one choice in a secondary setting, why people lose the response to ruxolitinib? And why are they affected in a negative way by fedratinib, particularly due to myelosuppression and anemia is the leading cause for stopping JAK inhibitor ruxolitinib for example. In a second-line setting, once you stop it, people are more anemic, more thrombocytopenic, they still don’t feel well, and they still have a big spleen. What do you do then when they have low counts? You can do momelotinib. It’s again non-myelosuppressive, improves the anemia, qualitatively different response than any other. And that’s why I think majority of the patients in the second-line setting, if the drug gets approved, will candidates and maybe given momelotinib over others.