EHA 2023 | Updated results from MANIFEST arm 2: pelabresib as add-on to ruxolitinib in myelofibrosis

So MANIFEST is an ongoing study that includes three different parts. First part was monotherapy with a BET inhibitor, pelabresib, and this is for patients that have progressed on a JAK inhibitor, ruxolitinib, and came off of it and now receive pelabresib as monotherapy. Part two is patients who are on ruxolitinib but who have had suboptimal response and they receive pelabresib as a second agent in addition to ruxolitinib, so it’s a combination therapy. And part three was combination therapy ruxolitinib and pelabresib in newly diagnosed myelofibrosis patients.

So, we will be focusing on part two, where patients are treated with pelabresib as an addition to ruxolitinib with a suboptimal response. And so, what the update shows is that there are multiple levels of responses. Patients enter part two of the study on ruxolitinib as two different cohorts: one if they’re transfusion dependent, and two if they have had symptomatic splenomegaly. And so, what is shown here is that patients who are treated with pelabresib who’re transfusion dependent, there’s about 30 to 40% response rate in terms of transfusion independence, which is a pretty significant result in this patient population with advanced myelofibrosis who are transfusion dependent. In addition, there is in general anemia response in this patient. For those patients that have splenomegaly, the current key endpoint is spleen response of 35% and that is seen in about 20% of patients. And again, this is a patient with a very advanced disease, and this is after multiple line of therapy.

In addition, patients are assessed for their symptom responses and there’s also significant improvement in patient symptoms in this overall cohort of patients. What’s also really important is that patients are able to remain on the study for a long time and continue to derive benefit from pelabresib therapy, or I should say from the combination therapy with pelabresib and ruxolitinib, where they’re maintaining their spleen response, maintaining their symptom response and maintaining the anemia response, which is also very exciting. And in general, this drug and the combination is well tolerated with adverse events that are similar to what we usually see in this patient population, with anemia and thrombocytopenia, as well as some gastrointestinal side effects that are, for most patients, easily controlled. So the drug is also well tolerated.

MANIFEST-2 study which is recently finished enrolling patients is a Phase III study which has taken patients with myelofibrosis that are JAK inhibitor-naive and is treating them in combination with JAK inhibitor ruxolitinib and pelabresib. The study is ongoing, and the results of that study will also be very exciting to see.