MPN Workshop of the Carolinas 2025 | The role of pacritinib in the treatment of myelofibrosis

I’m covering pacritinib, the third JAK inhibitor approved for myelofibrosis at this year’s MPN Workshop of the Carolinas. So pacritinib was approved in 2022. It was the third JAK inhibitor approved for myelofibrosis. And it has a very specific label. It’s for patients with platelets less than 50,000. Now this was a particular area of unmet need. So it absolutely, you know, fulfilled an important unmet need because less than 50,000, one, the prognosis of those patients is very bad, and two, we really didn’t have any agents at the time that we could safely use in these patients with ruxolitinib and fedratinib not generally considered safe in that patient population because of their myelosuppressive actions. And really, there was no data and you really needed a drug in that space. So when pacritinib came, it absolutely, you know, gave us something we could finally use for those patients. And to its credit, it has, you know, very decent rates of spleen and symptom response in that difficult population. And when you compare those rates to let’s say the overall rates with pacritinib you know in patients with higher platelets or or more of the the whole gamut of platelets what really stands out is that the rates of response spleen and symptoms in this severely thrombocytopenic population is really no worse, I mean numerically sometimes even better you know. 

So it seems to be doing something unique in this difficult population, in this difficult subset. And that may have to do with its non-JAK2 actions as well. So it is a JAK2 inhibitor. It does not inhibit JAK1, but it inhibits IRAK1 and, we have more recently learned, ACVR1. So it has some targets beyond JAK2 that may, one, explain its, you know, for example, its symptom benefit. So we’ve traditionally thought that you need JAK1 inhibition for symptom benefit, which it does not have. So maybe that’s due to the IRAK1 inhibition, for example. Maybe that’s also why it is less myelosuppressive or not myelosuppressive. And then finally, we’ve learned recently that it has an anemia benefit, which was sort of an after-the-fact realization. The drug had been around for some time. But in 2022, it was learned that it is also an ACVR1 inhibitor, which is thought to be why it has an anemia benefit.

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