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Momelotinib is a selective and orally available inhibitor of Janus kinase (JAK) 1, JAK2, and activin A type 1 receptor (ACVR1) that targets key drivers of myelofibrosis. The drug was investigated in two phase III studies, SIMPLIFY-1 and SIMPLIFY-2. In the SIMPLIFY-1 trial, patients with myelofibrosis, who were JAK inhibitor naïve (n = 432), were randomized 1:1 to 24 weeks of momelotinib or ruxolitinib. While in the SIMPLIFY-2 trial, patients with myelofibrosis, previously exposed to ruxolitinib (n = 156), were randomized 2:1 to momelotinib or best available therapy for 24 weeks. All patients from both studies were subsequently allowed to receive momelotinib for an extended period.1
Last year momelotinib has been granted Fast Track designation by the U.S. Food and Drug Administration, for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor.1,2
The long-term safety and dose intensity of momelotinib from > 550 patients across the two SIMPLIFY studies and their extended treatment periods were presented during the 25th European Hematology Association (EHA) virtual congress. Overall, > 90 patients continued to receive momelotinib for ≥ 3.5 years.2,3
The long-term safety data demonstrated a continued rapid and sustained increase in hemoglobin with momelotinib therapy, compared with a significant decrease observed in patients receiving ruxolitinib. Momelotinib treatment was also associated with a significant increase in platelet count. The improvements in hemoglobin and platelets were also observed in patients who switched from ruxolitinib.
In contrast to ruxolitinib, which frequently required dose reductions, in the majority of patients, the initial high dose intensity of momelotinib could be maintained over an extended treatment period. Furthermore, the long-term tolerability of momelotinib was favorable, with no new safety concerns, evidence of cumulative toxicity, or significant rates of high-grade hematological toxicities.
The authors believe that ‘’momelotinib may be an optimal therapy in myelofibrosis patients, in particular for areas with significant unmet needs such as those experiencing hematological toxicity and disease-related myelosuppression, which are common in this disease.’’
Momelotinib is also being compared with danazol in a phase III MOMENTUM clinical trial (NCT04173494) in patients with symptomatic and anemic myelofibrosis who have been treated previously with a JAK inhibitor.3
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