momelotinib + luspatercept

Combination therapy of **momelotinib** and **luspatercept** is currently being investigated for the treatment of transfusion-dependent myelofibrosis. Momelotinib is a small molecule Janus kinase (JAK) inhibitor, targeting JAK1 and JAK2, that blocks cytokine signaling associated with splenomegaly and constitutional symptoms, and has activity in reducing hepcidin, resulting in potential anemia improvement. Luspatercept is a recombinant fusion protein that acts as an activin receptor ligand trap, diminishing SMAD2/3 signaling and promoting late-stage erythropoiesis, leading to improved red blood cell production. The combination is hypothesized to provide synergistic or complementary benefits by targeting both early- and late-stage erythropoiesis, addressing anemia and transfusion burden in myelofibrosis patients. This combination is being studied in a Phase 2 clinical trial (NCT06517875) for efficacy and safety in transfusion-dependent myelofibrosis, including primary, post-polycythemia vera, and post-essential thrombocythemia forms[1][3][5][10].