As we know that patients treated with ruxolitinib for myelofibrosis, and indeed other JAK inhibitors, do obtain an important benefit, but that benefit is not always durable and it may not be as deep or as beneficial as we want it to be. In the MANIFEST study, we’ve been looking at pelabresib or CPI-0610, which is a BET or bromodomain inhibitor, which targets important relevant aspects of disease such as inflammation, NF kappa B, megakaryopoiesis, and erythropoiesis...
As we know that patients treated with ruxolitinib for myelofibrosis, and indeed other JAK inhibitors, do obtain an important benefit, but that benefit is not always durable and it may not be as deep or as beneficial as we want it to be. In the MANIFEST study, we’ve been looking at pelabresib or CPI-0610, which is a BET or bromodomain inhibitor, which targets important relevant aspects of disease such as inflammation, NF kappa B, megakaryopoiesis, and erythropoiesis.
In this study, which we have effectively added another year’s worth of data, we looked at adding pelabresib to patients who had not had an optimal response to ruxolitinib, or had failed that therapy. We divided patients according to whether they were transfusion-dependent or not. For the transfusion-dependent patients, our primary outcome was transfusion independence, and for the transfusion not dependent patients, our outcome was based around spleen and symptoms.
We saw meaningful responses for patients, and these have been durable. In addition, we saw no new safety outcomes, and that data contributed to some really interesting translational research, which was also presented at this meeting. Just to summarize that in brief, we saw that patients had reduction in VAF and reduction in bone marrow fibrosis, but they used artificial intelligence and digital morphology to look at megakaryocytes.
Now, your listeners will probably know that clustering of megakaryocytes is part of the diagnostic criteria for myelofibrosis, and with this drug we saw what we’ve called de-clustering of megakaryocytes, so their morphology becomes more normal and they move further apart into a more normal space. We were able to show that de-clustering correlated with spleen outcome and symptom benefit for patients.
This is a really interesting and important potential therapy for patients who’ve not had an optimum response. We also presented at this meeting results of JAK inhibitor-naive patients going on the combination together, showing nice deep responses for spleen and symptoms, and again, the additional disease modification markers that I discussed with you.
We have an ongoing study called MANIFEST-2 if the listeners are interested for patients who are JAK inhibitor-naive to randomize between pelabresib and ruxolitinib, or just Ruxolitinib alone. It’s a nice evolving story with a good consistent outcome for patients.