Danielle E. Marcotulli, APN: Dr McCloskey, momelotinib was recently submitted for FDA approval. Can you comment on some of the updated results from MOMENTUM?

James K. McCloskey II, MD: Sure. Well, first of all, momelotinib is a drug that probably people listening have been hearing about for a while. It is a JAK1 and [JAK2] inhibitor and was initially studied in a couple of different settings, but compared to ruxolitinib initially, we…hoped that this was going to be the next generation. It did fail in that trial to meet superiority to [ruxolitinib] initially, but we did see this anemia response. And that’s…where the ACVR1 story started, [it] was trying to get out why [we are] seeing anemia responses with momelotinib which we haven’t seen previously, and that really led to the MOMENTUM trial [NCT04173494]. This was a randomized phase 3 study that we did have at Hackensack [University Medical Center]. The primary end point of the trial really was total symptom score reduction, so a symptom response. So all these folks coming on had to be symptomatic, and then were going to be [randomly assigned] to either danazol or momelotinib, they also likewise had to be anemic and…the secondary end point of interest was anemia response. So it ended up being 195 patients came on [and we randomly assigned them to] either momelotinib or danazol. And what we saw is that we did see an improvement in total symptom score by 50% or more in 25% of the patients treated with momelotinib compared to only 9% of patients treated with danazol. We also saw a…transfusion independence rate…of 31% with momelotinib compared to 20% in danazol.

I think…that was…[a] surprising response rate even in the danazol arm for many of us, but it didn’t meet the criteria for statistical significance based on noninferiority to danazol and clearly didn’t meet the primary end point of total symptom score reduction. So we’ve seen [these] data continue, but…we did see updates…on this trial at ASH [the American Society of Hematology meeting] that showed that these responses seem to be durable over time. We also saw updated data on survival showing that responders seem to have an improved overall survival. Again, this isn’t surprising at all, and there’s always a selection bias. But I think that across the board and irrespective of which agent we’re talking about, it speaks to the value in clinical practice of offering these patients a drug to improve their cytopenias by improving cytopenias by stabilizing their disease, which seem to help people live longer, and that seems to be rather reproducible.

So again, I think these are drug[s]…waiting for approval. I think that it’s exciting to have new drugs in this space. And we’re getting a lot of interesting data, I mean, we just got the transfusion independence rates from [the phase 3] PERSIST-1 [trial; NCT01773187] with pacritinib. At ASH as well, [the MOMENTUM investigators] reported their results in severely thrombocytopenic patients showing improved survival in patients treated with momelotinib compared [with] danazol. Again, I think in the patient who’s practically cytopenic, I would advocate that all those people should be on more disease-directed therapy, and danazol is really something that we particularly use just for their anemia response, so not surprising. But I think that we continue to see both drugs exhibiting efficacy in these cytopenic patients.

And I think it’s going to be useful to have these drugs in our clinic. I think they are drugs that our patients are probably going to need both of them over time. I think that pacritinib is going to be and continue to be a drug that we would turn to first in our patients with more advanced cytopenias, who I’m really looking at their spleen volume particularly. If I have that patient [who] might have more isolated anemia and symptom management issues—they’re having a lot of itching, slight sweats, something of that nature—maybe we’ll turn to momelotinib-first…setting if they’re predominantly anemic with intact platelet counts. But I think the good news is that these drugs seem to have some overlap, and they’re going to have benefits for our patients over time. And we’ll continue to see the data as these drugs and the studies which led to their approvals continue to mature.

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