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Hello, my name is Ruben Mesa and I'm one of the hematologists who focus on myeloproliferative neoplasms at the Mayo Clinic in Scottsdale, Arizona. It's my pleasure, on behalf of the investigators of the Simplify One study, to present at this ASCO meeting the results of the study, this phase three trial of ruxolitinib versus momelotinib in patients naive to JAK inhibition.
The Simplify One study is based on the earlier studies where momelotinib was shown in single-dose studies to have improvements in splenomegaly symptoms, and anemia in patients with myelofibrosis. Potentially, for a variety of reasons, momelotinib has an impact on anemia. Part of these may include the differential effects of the JAK1 and JAK2 inhibition, but also potential impacts on decreasing hepcidin as a parallel effect of this agent.
The randomized phase three study was developed for the frontline setting in JAK naive patients. 432 patients that were JAK inhibitor naive with myelofibrosis were randomized between momelotinib and ruxolitinib in a double-blinded fashion with an open label component of momelotinib as a single agent. Patients were stratified according to red cell transfusion-dependence and their level of platelets.
The study had mixed results that I will go through. The goals of the study were to obtain non-inferiority of momelotinib verses ruxolitinib for reduction in splenomegaly, improvement in symptoms, and then if both of those endpoints were met, then analysis for superiority in the range of anemia.
For splenic response, momelotinib was found to be non-inferior to ruxolitinib, as shown on this slide. And that was statistically significant.
For symptom response rate, however momelotinib was found to not be non-inferior i.e. it was found to be inferior to ruxolitinib for symptom response. As we assess the symptoms, we assess them both in total symptoms in aggregate, as well as individual symptoms. This slide demonstrates the inferiority in terms of total symptoms score. In terms of individual symptoms, one is able to see that the greatest difference in the symptom impact profile was in the arena in itching and night sweats.
In terms of the differential impact on cytopenias that, as an isolated set of analysis, was favorable for momelotinib having better data for stability in the hemoglobin as well as stability in the platelet count.
Prior studies had raised peripheral neuropathy as a potential toxicity of this agent. And although it was slightly higher in patients with momelotinib ... 10% on momelotinib, 5% in ruxolitinib ... this did not lead to any discontinuations on the trial, and these did not rise to the level of grade three or above.
Our conclusion to the study was that momelotinib was not inferior to ruxolitinib for splenic response. However it failed to meet the key non-inferiority criteria for the secondary endpoint of symptom response using the self-reported tool. Patients treated with momelotinib did have improvement in anemia and transfusion requirements compared to those with ruxolitinib, however this endpoint did require meeting both of the prior endpoints to be fully evaluable. No new safety signals were detected. And peripheral neuropathy occurred and 10% of momelotinib patients versus 5% of ruxolitinib. The drug is active. The results of this study were mixed, so discussion is ongoing regarding further steps for this agent.
Thank you very much for your attention on this video.