A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis

Vikas Gupta, Ruben A. Mesa, Michael W N Deininger, Candido E Rivera, Shireen Sirhan, Carrie Baker Brachmann, Helen Collins, Jun Kawashima, Yan Xin, Srdan Verstovsek

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35 Scopus citations


Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, nonrandomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post–polycythemia vera/post–essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
Issue number1
StatePublished - 2017


ASJC Scopus subject areas

  • Hematology

Cite this

Gupta, V., Mesa, R. A., Deininger, M. W. N., Rivera, C. E., Sirhan, S., Brachmann, C. B., Collins, H., Kawashima, J., Xin, Y., & Verstovsek, S. (2017). A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis. Haematologica, 102(1), 94-102. https://doi.org/10.3324/haematol.2016.148924