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A JAK inhibitor that also blocks the anaemia-driving ACVR1 pathway improved symptoms and spleen size without worsening, and often improving, anaemia in previously treated patients.
MOMENTUM randomised 195 symptomatic, anaemic patients with myelofibrosis previously treated with a JAK inhibitor to momelotinib or danazol (2:1) for 24 weeks, after which danazol patients could cross over. The primary endpoint was a 50% or greater reduction in total symptom score at week 24. This was achieved by 25% versus 9%; transfusion independence at week 24 was 30% versus 20%, meeting non-inferiority, and spleen volume reduction of at least 35% was 22% versus 3%. Momelotinib inhibits JAK1, JAK2 and ACVR1, the last of which lowers hepcidin and improves iron availability. Grade 3 or higher thrombocytopenia and infections were the main toxicities. The drug was approved in 2023 specifically for myelofibrosis with anaemia.
MOMENTUM addressed the biggest gap left by ruxolitinib: patients whose anaemia makes standard JAK inhibition hard to give. Momelotinib is now the preferred option for anaemic, previously treated myelofibrosis and is being adopted in first line for anaemic patients. The absolute symptom benefit is modest and durable disease modification has not been shown.
Shares Pacritinib, Momelotinib, JAK2, Primary myelofibrosis.
Shares Pacritinib, Momelotinib, JAK2, Ruxolitinib.
Shares COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis, Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Momelotinib, Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Pacritinib, Momelotinib, Ruxolitinib, Primary myelofibrosis.
Shares JAK2, Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Momelotinib, Primary myelofibrosis, GSK, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Primary myelofibrosis, GSK, Myeloproliferative neoplasms (PV, ET, myelofibrosis).