EHA 2026 | The evolving role of momelotinib in myelofibrosis: insights from post hoc analyses of pivotal trials

Yeah, momelotinib has been, it’s a relatively new player still to the MF treatment landscape approved in 2023, but clearly has had a huge impact already because this is a drug that is a JAK1, JAK2 inhibitor and also improves anemia through a different mechanism, which is the inhibition of ACVR1 and down regulation of hepcidin. So this obviously is a very welcome addition to the field because, you know, we’ve had JAK inhibitors for 15 years, but anemia has been a problem. And JAK inhibitors, particularly ruxolitinib, fedratinib, do not typically improve anemia and they actually worsen anemia. So, in that regard, the entry of momelotinib has been a very welcome addition where you can get the spleen and symptom benefits, but you can also get anemia benefit. 

So, I think in terms of its evolving role, you know, of course, it’s used widely in the post-ruxolitinib setting, but I think we’re also seeing increasing use in the frontline setting. And there’s actually been some very interesting post hoc analyses done of the pivotal trials like, you know, SIMPLIFY-1 and MOMENTUM. SIMPLIFY-1 was a frontline trial. Momentum was a second line trial. But there’s these post hoc analyses that have been done that have really given us a lot of insights into where this drug best fits, you know. And I think besides the obvious, which is, you know, anemic patients in second line, I think we are learning that in frontline, where you cannot, let’s say, deliver the full dose of ruxolitinib because of cytopenias, momelotinib has an increasing role, you know, where platelets are less than 200, hemoglobin less than 10. In these situations, momelotinib could be a very reasonable frontline choice. And also, you know, for example, in settings where, you know, you’ve got low hemoglobin to start with, we’ve seen now post hoc data again from SIMPLIFY-1, MOMENTUM, showing that if you improve that hemoglobin to over 10, that has a survival correlation. So, all these types of analyses are really informing us better as to how to use momelotinib. 

With regards to the specific analysis we are presenting this year at EHA, we wanted to look at specifically the intermediate-one risk patients in SIMPLIFY-1 and MOMENTUM as opposed to the intermediate two and high risk patients. And this type of analysis has been done with RUX in the COMFORT trial. So, it just made sense to specifically look at the intermediate one subgroup in the momelotinib phase three trials. And I think basically what we saw is that the benefits were maintained. In most cases, the benefits were higher in intermediate one than in intermediate two and high. Not entirely uniformly, but in most cases, the spleen and symptom responses were higher in intermediate one, which makes sense because it’s a less sick population. It’s kind of an earlier stage of the disease, if you will. So those were the main takeaways from that particular abstract.

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