ASH 2025 | Preliminary analysis of the FEDORA trial: fedratinib plus ropeginterferon alfa-2b in myelofibrosis

FEDORA is an investigator-led trial looking at a combination of fedratinib and ropeginterferon alpha-2b, which I will call ropeg. The idea was that this may have superior efficacy in treating patients, but we have to do the trial first to see if it’s tolerable in combination. So patients started on a dose of fedratinib, establishing them on a JAK inhibitor, as would be standard practice. And then after four weeks or more, depending on toxicity, they went on increasing doses of ropeg up to a maximum of 250 micrograms, thus acting as their own controls. The patient population were what I would call a pure treatment-naive group of patients. So they were judged to need treatment for their myelofibrosis and had to be JAK2 positive. 

So I presented an analysis from a data cut at the end of October. So the bottom line is that the primary endpoint, which was the number of patients we were sustained on the combination at the four-month period was achieved, i.e. 27 out of 30 tolerated the combination. That is 87% and it had to be 80% or above to achieve the primary outcome. I then presented some other early data showing that the blood counts were stable, there were reductions in spleen size and there was some early improvements on symptoms and, perhaps most excitingly, in those where we were able to do some JAK2 VAF analysis we saw quite a lot of reductions in the JAK2 VAF, even at this early point. So, in summary, the trial met its primary endpoint. It is obviously ongoing, but there are encouraging signs of efficacy as regards spleen size symptoms and stable blood counts, and decreases in the JAK2 VAF. Obviously, then long-term follow-up to complete the trial is interesting and exciting.

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