A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia

Srdan Verstovsek, Stephane Courby, Martin Griesshammer, Ruben Mesa, Carrie Baker Brachmann, Jun Kawashima, Julia D. Maltzman, Lixin Shao, Yan Xin, Daniel Huang, Ashish Bajel

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in patients with primary and secondary myelofibrosis. This phase 2, open-label, randomized study evaluated the efficacy and safety of oral once-daily momelotinib (100 mg and 200 mg) for the treatment of polycythemia vera (PV) and essential thrombocythemia (ET). The primary endpoint for PV was overall response rate (ORR), defined as the proportion of patients with hematocrit <45%, white blood cell count <10 × 109/L, platelet count ≤400 × 109/L, and resolution of palpable splenomegaly, each lasting ≥4 weeks. The definition of ORR for ET excluded the hematocrit component. A total of 39 patients (28 PV, 11 ET) were enrolled, with 28 patients receiving ≥12 weeks of treatment. The study was terminated due to limited efficacy. Two patients (ORR 5.1%) met the primary efficacy endpoint (both PV 200 mg). Predose plasma levels of momelotinib were stable over time. A total of 31 (79.5%) patients experienced momelotinib-related adverse events (AEs), the most frequent being headache (23.1%), dizziness (18.0%), somnolence (15.4%), nausea (15.4%), and fatigue (15.4%). Three patients experienced serious AEs (7.7%), with 1 considered related to momelotinib (dyspnea). Peripheral neuropathy occurred in 7 (17.9%) patients (4 PV, 3 ET).

Original languageEnglish (US)
Pages (from-to)11-17
Number of pages7
JournalLeukemia Research
Volume60
DOIs
StatePublished - Sep 1 2017
Externally publishedYes

Fingerprint

Essential Thrombocythemia
Polycythemia Vera
Hematocrit
Primary Myelofibrosis
N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
Splenomegaly
Dizziness
Peripheral Nervous System Diseases
Platelet Count
Leukocyte Count
Dyspnea
Nausea
Fatigue
Headache
Safety

Keywords

  • Essential thrombocythemia
  • Momelotinib
  • Phase 2 study
  • Polycythemia vera

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia. / Verstovsek, Srdan; Courby, Stephane; Griesshammer, Martin; Mesa, Ruben; Brachmann, Carrie Baker; Kawashima, Jun; Maltzman, Julia D.; Shao, Lixin; Xin, Yan; Huang, Daniel; Bajel, Ashish.

In: Leukemia Research, Vol. 60, 01.09.2017, p. 11-17.

Research output: Contribution to journalArticle

Verstovsek, S, Courby, S, Griesshammer, M, Mesa, R, Brachmann, CB, Kawashima, J, Maltzman, JD, Shao, L, Xin, Y, Huang, D & Bajel, A 2017, 'A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia', Leukemia Research, vol. 60, pp. 11-17. https://doi.org/10.1016/j.leukres.2017.05.002
Verstovsek, Srdan ; Courby, Stephane ; Griesshammer, Martin ; Mesa, Ruben ; Brachmann, Carrie Baker ; Kawashima, Jun ; Maltzman, Julia D. ; Shao, Lixin ; Xin, Yan ; Huang, Daniel ; Bajel, Ashish. / A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia. In: Leukemia Research. 2017 ; Vol. 60. pp. 11-17.
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abstract = "Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in patients with primary and secondary myelofibrosis. This phase 2, open-label, randomized study evaluated the efficacy and safety of oral once-daily momelotinib (100 mg and 200 mg) for the treatment of polycythemia vera (PV) and essential thrombocythemia (ET). The primary endpoint for PV was overall response rate (ORR), defined as the proportion of patients with hematocrit <45{\%}, white blood cell count <10 × 109/L, platelet count ≤400 × 109/L, and resolution of palpable splenomegaly, each lasting ≥4 weeks. The definition of ORR for ET excluded the hematocrit component. A total of 39 patients (28 PV, 11 ET) were enrolled, with 28 patients receiving ≥12 weeks of treatment. The study was terminated due to limited efficacy. Two patients (ORR 5.1{\%}) met the primary efficacy endpoint (both PV 200 mg). Predose plasma levels of momelotinib were stable over time. A total of 31 (79.5{\%}) patients experienced momelotinib-related adverse events (AEs), the most frequent being headache (23.1{\%}), dizziness (18.0{\%}), somnolence (15.4{\%}), nausea (15.4{\%}), and fatigue (15.4{\%}). Three patients experienced serious AEs (7.7{\%}), with 1 considered related to momelotinib (dyspnea). Peripheral neuropathy occurred in 7 (17.9{\%}) patients (4 PV, 3 ET).",
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AU - Brachmann, Carrie Baker

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AU - Maltzman, Julia D.

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AU - Xin, Yan

AU - Huang, Daniel

AU - Bajel, Ashish

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