The U.S. Food and Drug Administration has approved momelotinib (Ojjaara) for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia), in adults with anemia.
Myelofibrosis is a rare cancer characterized by extensive scarring of the bone marrow and the disruption of normal blood cells production. This leads to severe anemia that can cause weakness and fatigue.
Momelotinib is a potent inhibitor of Janus kinase 1 (JAK1), Janus kinase 2 (JAK2) and Activin A receptor, type I (ACVR1). This unique profile results in clinical activity against three hallmark features of myelofibrosis – anemia, constitutional symptoms and splenomegaly.
Momelotinib’s anemia benefit is primarily achieved through direct inhibition of ACVR1 leading to a decrease in circulating hepcidin. Hepcidin is often markedly elevated in myelofibrosis and contributes to an iron restricted anemia. By lowering hepcidin, a corresponding increase in serum iron occurs with consequent clinically relevant increases in hemoglobin and red blood cells due to increased iron availability for erythropoiesis. This is significant as other JAK-inhibitors used to manage myelofibrosis often worsen patients’ anemia.
The approval was largely based on data from two phase 3 studies – the pivotal phase 3 MOMENTUM study involving patients (N=195) with myelofibrosis who had previously been treated with a JAK inhibitor and the phase 3 SIMPLIFY-1 trials involving treatment naïve patients with myelofibrosis. Details of the SIMPLIFY-1 study are currently limited but results of the MOMENTUM study was published in Lancet. In that trial, 195 patients with myelofibrosis were randomly assigned to receive momelotinib (200 mg orally once per day) plus danazol (n=130) or danazol alone (n=65 ). At the end of the 24 week study, 25% of the momelotib group reported a 50% or more reduction in their total symptom score (TSS) compared to 9% in the control group.
Details of the MOMENTUM study were shared with CheckRare by Srdan Verstovsek, MD, PhD, Medical Oncologist and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. (see below)
The most common adverse reactions (≥20% in either study) are thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
To learn more about myelofibrosis and other rare cancers, visit https://checkrare.com/diseases/cancers
Verstovsek S, Gerds AT, Vannuchi AM et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023; 401: 269-280. doi.org/10.1016/S0140-6736(22)02036-0.