MPN-147: Dynamic and Time-To-Event Analyses Demonstrate Marked Reduction in Transfusion Requirements for Janus Kinase Inhibitor-Naïve Myelofibrosis Patients Treated with Momelotinib Compared Head to Head with Ruxolitinib

Background: Systemic inflammation integral to the pathogenesis of myelofibrosis (MF) leads to increased ACVR1 activity and hepcidin production, resulting in perturbed iron homeostasis and iron-restricted anemia. Chronic, progressive anemia is a key hallmark feature of MF. Anemia and transfusion dependency (TD) are strongly predictive of reduced survival. Momelotinib (MMB) is a potent, orally bioavailable, small-molecule inhibitor of JAK1, JAK2, and ACVR1. MMB's inhibition of ACVR1, unique amongst the JAK inhibitor (JAKi) class, leads to reduction of hepcidin, restoring iron homeostasis and RBC production and alleviating anemia and transfusion dependency in patients with MF. Objective: To explore the relative burden of transfusions for MMB vs RUX. Methods: SIMPLIFY-1 (S1) was a double-blind, randomized, Phase 3 study of MMB vs RUX in intermediate-/high-risk JAKi-naive patients with MF (n=215 MMB, 217 RUX). Retrospective analyses of data from the randomized treatment phase (RT; 24 weeks) were performed using a variety of novel dynamic anemia benefit endpoints including time until transfusion and overall intensity of transfusions across time. Results: Kaplan-Meier estimates of the proportion of patients who required zero units transfused during the RT period were 73% and 46% for MMB and RUX respectively (p Conclusions: Since transfusion burden is of significant concern to clinicians and patients, these novel analyses of the anemia benefits of MMB are important additions to standard analytic methods. Combined with additional data from the SIMPLIFY studies, they demonstrate that MMB is able to address the three hallmark features of MF, namely anemia, constitutional symptoms and splenomegaly, differentiating it from other JAKi. Momelotinib is the only clinical stage JAKi to possess potent ACVR1 inhibitory activity, resulting in improvement of anemia.