Momelotinib for the treatment of myelofibrosis

ABSTRACT

Introduction: The abnormally activated JAK-STAT pathway plays a central role in the pathogenesis of BCR/ABL-negative myeloproliferative neoplasms (MPNs), simultaneously providing a theoretical and clinical basis for the development of small-molecule compounds targeting JAK. The first approved drug, ruxolitinib, demonstrated a rapid and durable improvement of symptoms and splenomegaly accompanied with better overall survival in myelofibrosis (MF) patients. However, ruxolitinib-related adverse effects and resistance are limitations, so there is an urgent need to develop new JAK inhibitors to retain the efficacy of ruxolitinib and avoid its deficiency.

Areas covered: This review discusses the preclinical and clinical studies of momelotinib (MMB) aiming to gain a deeper understanding of the advantages and clinical limitations of this drug.

Expert opinion: The clinical trial data available thus far indicate that MMB is not inferior to ruxolitinib in spleen response and symptoms response, with the improvement of anemia surprising. The only obstacle that may slowdown its approval is treatment-emerged peripheral neuropathy (PN). If we can minimize MMB’s treatment-related PN by administration optimization, MMB promises to be a good choice of individualized treatment for MF patients mainly manifesting as anemia.

KEYWORDS:

• Myelofibrosis
• MPN
• JAK inhibitor
• Momelotinib
• anemia
• peripheral neuropathy

Box 1. Drug summary box

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article received grant support from the Social Development Science and Technology Fund of Shaanxi Province [2016SF071] provided to H Tang.