James K. McCloskey II, MD: And so, Danielle I think we … touched upon this, the importance of considering anemia and how that might impact our patients with myelofibrosis and some of the improvement in anemia that we’ve seen with pacritinib. Could you talk about the way that anemia impacts our patients, the importance around management of anemia, and maybe the mechanism of action of anemia in myelofibrosis?

Danielle E. Marcotulli, APN: We’ve seen the role of ACVR1 in these patients … And we know that by inhibiting it we could actually improve anemia. And in some of the retrospective data that we saw in some of these trials, we saw that pacritinib could be a potent inhibitor of ACVR1, which therefore improves anemia in some of our patients. And previously I think we’ve all had difficulty treating these patients because of dose-limiting cytopenias, and how they feel [is] very much impacted by anemia. So seeing that this drug could potentially improve their anemia and may not worsen it, was very exciting for us.

James K. McCloskey II, MD: This is a cytopenia that really dramatically impacts our patient’s quality of life. It’s the cytopenia that leaves them feeling pretty crummy, it leaves them tethered to our office. And in every study we’ve ever done, the development of anemia is associated with a decline in survival. Improvement in anemia and restoration of inadequacies have time and time again been shown to be associated with improved overall survival and better outcomes. I think [it] is important to keep [cytopenia] in mind. We did see this year work presented: A couple of different abstracts, first looking at PERSIST-2 as I mentioned, and transfusion independence rates. And what we saw was that, for patients treated with pacritinib transfusion, independence was achieved in 24% of patients treated with [pacritinib] compared with 5% of patients treated with best available therapy if we use simplified criteria. If we use the criteria, it actually is 37% compared with 7%. Depending on how we measure transfusion independence, we do see these patients coming off of transfusions. We also see patients who are experiencing an increase in their hemoglobin, an improvement in the hemoglobin from baseline. And then lastly, we saw some data to try to explain this, and I think that ever since we saw that early data in PERSIST-1 … there’s been a desire to want to explain it.

Obviously, we’d like to understand that so that we can anticipate response rates in patients but also so that we could apply that understanding to future studies and possible combination studies. As Danielle mentioned, we did see that this drug is capable of inhibiting ACVR1, which we know is the mechanism of action by which momelotinib may offer improvement in anemia as well … I personally think it’s probably a combination of factors. I think in some component it might be the lack of JAK1 inhibition and may have some component of IRAK inhibition. We are studying IRAK inhibitors in low-grade MDS [myelodysplastic syndromes]. for overseeing responses in anemia there. But I think what was interesting was some of the data … showing that, yes, pacritinib does inhibit ACVR1 and potentially inhibit it to a greater degree than momelotinib; possibly as much as a 4-fold increase. I think that obviously [these are] limited data, that did require some mathematic modelling. But it does get to the mechanism of action to some degree. For me in the clinic, I think that the most important thing is that it’s doing what I’m seeing it do, more than why. As a clinician, as an academician, and as someone looking at the next batch of clinical trials, we certainly want to understand more of why [we are] seeing this.

Transcript is AI-generated and edited for clarity and readability.