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EHA 2026 | Insights into the mechanisms and treatment responses of the PIM-1 kinase inhibitor, nuvisertib in MF
Prithviraj Bose, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, shares insights into the mechanisms behind nuvisertib, a PIM-1 kinase inhibitor, which has been investigated in trials in the post-JAK inhibitor setting for patients with myelofibrosis (MF). Dr Bose highlights that nuvisertib has been observed to inhibit ACVR1, which may contribute to improvements in anemia, and notes that, in combination with ruxolitinib, it may also counteract ruxolitinib-associated anemia. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
So, nuvisertib is a PIM-1 kinase inhibitor and it’s been in trials for some time now in the post-JAK setting as well as in combination with both ruxolitinib and momelotinib. So, with ruxolitinib, there’s an add-on cohort. With momelotinib, there is a cohort where you start with both momelotinib and nuvisertib in people who have been previously treated with JAK inhibitors. So, those are the three cohorts...
So, nuvisertib is a PIM-1 kinase inhibitor and it’s been in trials for some time now in the post-JAK setting as well as in combination with both ruxolitinib and momelotinib. So, with ruxolitinib, there’s an add-on cohort. With momelotinib, there is a cohort where you start with both momelotinib and nuvisertib in people who have been previously treated with JAK inhibitors. So, those are the three cohorts. Nuvisertib alone, momelotinib and nuvisertib, or nuvisertib added to rux. But what is new in this poster at this year’s EHA is that there’s a new mechanism of nuvisertib that was just recently uncovered, which is the inhibition of ACVR1. So, like we know for momelotinib, we believe that that’s its mechanism of anemia benefit, where we, you know, inhibit ACVR1, down-regulate hepcidin. That has now been found to be the case also with nuvisertib, which was better known as a PIM1 kinase inhibitor. But now we’re learning that it’s a PIM1 and ACVR1 inhibitor. So perhaps we would hope to see, especially in this momelotinib-nuvisertib combo cohort, maybe we would see an incremental or additive impact on the anemia with both drugs doing this kind of the same thing in regards to the ACVR1 inhibition. Also, when you add nuvisertib to rux, this mechanism might be valuable in counteracting some of the rux-induced anemia. So this is just a novel facet to nuvisertib. So, nuvisertib is a PIM-1 kinase inhibitor and it’s been in trials for some time now in the post-JAK setting as well as in combination with both ruxolitinib and momelotinib. So, with ruxolitinib, there’s an add-on cohort. With momelotinib, there is a cohort where you start with both momelotinib and nuvisertib in people who have been previously treated with JAK inhibitors. So, those are the three cohorts. Nuvisertib alone, momelotinib and nuvisertib, or nuvisertib added to rux. But what is new in this poster at this year’s EHA is that there’s a new mechanism of nuvisertib that was just recently uncovered, which is the inhibition of ACVR1. So, like we know for momelotinib, we believe that that’s its mechanism of anemia benefit, where we, you know, inhibit ACVR1, down-regulate hepcidin. That has now been found to be the case also with nuvisertib, which was better known as a PIM1 kinase inhibitor. But now we’re learning that it’s a PIM1 and ACVR1 inhibitor. So perhaps we would hope to see, especially in this momelotinib-nuvisertib combo cohort, maybe we would see an incremental or additive impact on the anemia with both drugs doing this kind of the same thing in regards to the ACVR1 inhibition. Also, when you add nuvisertib to rux, this mechanism might be valuable in counteracting some of the rux-induced anemia. So this is just a novel facet to nuvisertib.
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