ASH 2024 | An update on a Phase II study of fedratinib in MDS/MPN overlaps and chronic neutrophilic leukemia

You know, this was an investigator-initiated trial that we really tried to investigate an agent, fedratinib, that we think is quite potent and very effective in patients with myelofibrosis. It hasn’t really found a true niche in that disease state, probably owing to kind of the previous approval of ruxolitinib as well as some toxicity profile, but given its potency, I think we thought it made sense to study this in a group of patients that are often overlooked and excluded from many clinical trials, which are patients that have MDS/MPN overlaps. And so we really kind of performed this multi-center, small multi-center study amongst four centers, really for this specific group of patients, including those that had atypical CML, MDS/MPN-RS-T, chronic neutrophilic leukemia, as well as MDS/MPN unclassifiable. And to enroll in the trial, patients really just had to have proliferative features that we thought could benefit from this agent. 

And what we saw now that the trial is fully accrued, though we don’t have final results as the final patient went on in October of 2024, is that the drug actually performs quite well in this group of patients. So we’re able to see high rates of spleen responses between 35 and 40 percent, symptom responses of 50 percent, and really durable therapy, even though we certainly have limited follow-up at this point, but median follow-up, median time on therapy is around 10 to 11 months right now. So I think very encouraging early findings in this group. We do know that fedratinib may be uniquely positioned for treating this group of patients, given the fact that it is a JAK2 inhibitor, but also has interesting properties where it inhibits BRD4, so, it’s kind of a BET inhibitor protein associated with NF-kappa B inflammation, as well as potently suppresses MYC in the bone marrow. And we know that MYC may be particularly implicated in these proliferative MPN-type diseases that don’t have a JAK-STAT mutation, as well as patients that have SETBP1 mutations, which are very common in this group. So very excited to kind of see how this trial plays out now that it’s fully accrued, present final data, but certainly very encouraging so far.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.