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Momelotinib is a novel, orally bioavailable inhibitor of JAK1, JAK2, and ACVR1. This combined profile is unique amongst currently approved and emerging JAK inhibitor-based therapeutics. Momelotinib is an investigational agent that has not been approved by any regulatory agency.
Data from worldwide clinical trials involving more than 800 patients with MF—across the continuum of intermediate/high risk patients including JAKi-naïve and previously JAKi-treated subjects—suggest that momelotinib has the potential to improve constitutional symptoms and splenomegaly while also addressing the chronic anemia and transfusion dependency associated with the disease. The most commonly reported grade 3 or 4 adverse events observed in randomized Phase 3 trials with momelotinib include thrombocytopenia, anemia, diarrhea and neutropenia.
It is hypothesized that momelotinib’s anemia impact may be achieved through direct inhibition of ACVR1, leading to a decrease in circulating hepcidin. Hepcidin is often markedly elevated in MF and contributes to iron restricted anemia. By lowering hepcidin, a corresponding increase in available serum iron occurs with consequent clinically relevant increases in hemoglobin and red blood cells.15
15 Asshoff M, Petzer V, Warr M, et al. 2017. Blood. 129(13):1823-1830.
Oh S, Talpaz M, Gerds A, et al. 2020. Blood Advances. 4(18):4282-4291.
More than 820 patients with myelofibrosis have received momelotinib during its development, including a number of patients who remain on treatment since the start of the original Phase 2 studies initiated a decade ago. The data presented at EHA 2020 and ASH 2020 draw from more than 550 patients across the two previously conducted SIMPLIFY Phase 3 studies and their subsequent ongoing extended treatment periods, and further demonstrate the potential anemia benefits and favorable hematological safety profile and long-term term tolerability of momelotinib.