Clinical Summary: 

• Design/Population: Post hoc analyses of the phase 3 SIMPLIFY-1 and MOMENTUM trials evaluated outcomes with momelotinib in patients with intermediate-1 versus intermediate-2/high-risk myelofibrosis. SIMPLIFY-1 enrolled JAK inhibitor–naïve patients, while MOMENTUM enrolled previously treated, anemic patients with myelofibrosis.
• Key Outcomes: Momelotinib demonstrated spleen, symptom, and anemia benefits across all risk categories. Response rates for several endpoints, including symptom improvement and transfusion independence, were numerically higher among patients with intermediate-1–risk disease, suggesting greater benefit when treatment is initiated earlier in the disease course.
• Clinical Relevance: These findings support the use of momelotinib across the full spectrum of approved risk categories and suggest that earlier treatment may optimize clinical outcomes in myelofibrosis.

Prithviraj Bose, MD, MD Anderson Cancer Center, Houston, Texas, discusses post hoc analyses from the phase 3 SIMPLIFY-1 and MOMENTUM trials evaluating the impact of disease risk category on outcomes with momelotinib. Although momelotinib is approved for patients with intermediate- or high-risk myelofibrosis and anemia, data specifically examining patients with intermediate-1–risk disease have been limited.

The analyses demonstrated that momelotinib provides clinically meaningful spleen, symptom, and anemia benefits regardless of risk category, with several efficacy endpoints appearing numerically more favorable in patients with intermediate-1–risk disease. These findings suggest that earlier intervention with momelotinib may improve outcomes while reinforcing its utility across the broad range of patients for whom the therapy is approved.

Dr Bose presented these results at the European Hematological Association (EHA) Annual Meeting in Stockholm, Sweden. 

Transcript: 

I'm Prithvi Bose, professor and co-section head of the MPN section in the leukemia department at MD Anderson Cancer Center in Houston, Texas. I'm going to talk to you a little bit about some analyses that were presented at EHA 2026 in Stockholm on the SIMPLIFY-1 and MOMENTUM trials.

Now, as you recall, SIMPLIFY-1 and MOMENTUM were the 2 large phase 3 trials that supported the approval of momelotinib for the treatment of myelofibrosis with anemia. SIMPLIFY-1 was a large head-to-head phase 3 trial of momelotinib versus ruxolitinib in the frontline setting, so the JAK inhibitor–naïve setting. In this trial, the spleen response rates with the 2 drugs were similar. Momelotinib was noninferior to ruxolitinib, while noninferiority was not met for symptom response. Now, with regard to all the anemia parameters, as you recall, momelotinib was better than ruxolitinib, and this refers to transfusion independence, number of units transfused, etc. 

MOMENTUM was a second-line study in which patients previously treated with JAK inhibitors were randomized to momelotinib or danazol. All patients had to be anemic, that is, have a hemoglobin less than 10 at baseline, and a symptom score of at least 10 at baseline. These patients were randomized 2:1 to momelotinib or danazol, and momelotinib was superior for both spleen and symptoms. When it came to the anemia end points, momelotinib was better as well. Transfusion independence was actually powered for noninferiority, so momelotinib was noninferior to danazol for transfusion independence, although numerically it was superior. All the other anemia parameters also favored momelotinib. So this was a trial that met all of its end points. Importantly, after crossover, after 24 weeks, the danazol patients, in terms of their anemia, their response rates improved and approached those of the patients originally randomized to momelotinib.

Now, with that background, just a few quick words on 2 analyses that were presented at EHA.

One looked at patients from both SIMPLIFY-1 and MOMENTUM, and compared how intermediate-1 patients fared versus intermediate-2 or high-risk patients in both trials. Really, it ends up being a lot of different comparisons because you've got spleen response, symptom response, and anemia response rates in intermediate-1 versus intermediate-2 and high-risk patients. But the bottom line is that overall the benefits of momelotinib were maintained. That is to say, in both SIMPLIFY-1, which is frontline, and MOMENTUM, which is second line, the response rates in terms of spleen and symptoms were very similar across the intermediate-1 and intermediate-2/high-risk subgroups. There was actually a trend toward response rates being higher in intermediate-1 patients, which makes sense because they're at an earlier stage of disease, a less advanced stage of disease. So it was no surprise that some of the response rates were actually higher in intermediate-1 than in intermediate-2 and high, although that was not the case for every end point that was analyzed.

The other analysis—again, these are all post hoc analyses—was from SIMPLIFY-1 only, not MOMENTUM. Here, the focus was on what happened to symptoms when patients crossed over from ruxolitinib to momelotinib. Recall that in SIMPLIFY-1 this happened essentially in all patients after 6 months (24 weeks) when the patients in the ruxolitinib arm crossed over to momelotinib. This is, of course, in the context of what is called ruxolitinib discontinuation syndrome, which is this flare of splenomegaly and symptoms that can occur when one stops ruxolitinib. So it was of interest to see whether this occurred or not. Now, in a prior analysis, it had already been shown that this really does not happen in the context of switching from ruxolitinib to momelotinib. That analysis, also from SIMPLIFY-1, showed that one could safely switch from ruxolitinib to momelotinib without the need for a taper or a washout. This more comprehensive analysis that we presented at EHA really confirmed those same conclusions—that the switch from ruxolitinib to momelotinib in the ruxolitinib arm of SIMPLIFY-1 was not associated with any sort of rebound in symptoms that would be concerning for a flare or the so-called ruxolitinib discontinuation syndrome. 

So really, the message for clinicians would be that when switching from ruxolitinib to momelotinib, there really isn't any need to taper the ruxolitinib or overlap the 2 drugs, as we sometimes do with some of the other JAK inhibitors that have a longer half-life or different effects on JAK1 and JAK2. Here, it seems to be fairly straightforward to switch patients from ruxolitinib to momelotinib without any washout, taper, or overlap.

Source: 

Bose P, O’Connell C, McLornan D, et al. Outcomes with momelotinib in patients with intermediate-1– vs intermediate-2–/high-risk myelofibrosis: Post hoc analyses of the phase 3 SIMPLIFY-1 and MOMENTUM trials. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-3428.