EHA 2025 | 72-week results from MANIFEST-2: pelabresib plus ruxolitinib in JAK inhibitor-naive myelofibrosis

The MANIFEST-2 study assessed pelabresib, which is a BET inhibitor, targeting some of the key pathways, including NF-kappa B in myelofibrosis. And we’ve had a longstanding interest now for over 10 years, actually, recruiting patients into studies with pelabresib. And what was really important to see in the 72-week data for MANIFEST-2, which was an upfront study comparing patients who are still ongoing in a randomization between ruxolitinib plus or minus pelabresib or placebo, was that we continued to see almost double the number of patients achieving both SVR 35 and TSS50 out at week 72. We also saw very nice data with bone marrow fibrosis reduction, ongoing good safety signal, slightly more dysgeusia, slightly more thrombocytopenia, but otherwise really a balance with adverse events, despite adding a second agent. Of course, the kind of question of the moment is the issue with blast phase and accelerated phase, whether there were more of those in patients treated with pelabresib. And actually, it looks like at the week 72 slot that actually the patients on the control arm are sort of catching up. So suggesting even more that this was probably, you know, bad luck and a blip, even though, you know, there were intermediate one risk patients in this study, these patients still can get this devastating consequence. The other important data that we showed in this presentation, which came from Alessandro Vannucchi was that overall progression-free and leukaemia-free survival were not adverse and if anything possibly look like they might be coming, you know, better for the combination although it’s probably too early to say that. Still very interesting looking for the week 96 data now and super important.

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