Fedratinib: a pharmacotherapeutic option for JAK-inhibitor naïve and exposed patients with myelofibrosis.

Abstract

INTRODUCTION:

Ruxolitinib is the most commonly used JAK-inhibitor (JAKi) for the management of symptoms related to splenomegaly and cytokine-mediated inflammation in patients with myelofibrosis (MF), but is limited by variable durability of response with most patients experiencing failure after 2-3 years. Long-term data on other approved JAKi, fedratinib and pacritinib, are not available due to the clinical hold put on pivotal trials for toxicity concerns.

AREAS COVERED:

Following the initial hold for concern of Wernicke's encephalopathy, fedratinib was approved by the Food and Drug Administration (FDA) in 2019 for MF. We review the data available from early, and late phase critical trials, outline a role for fedratinib in the current treatment landscape of MF, and highlight the knowledge gaps in optimizing use of fedratinib.

EXPERT OPINION:

The JAKARTA and JAKARTA2 trials established efficacy in spleen volume response (SVR) and symptom reduction in JAKi-naïve and ruxolitinib-exposed MF patients, respectively. Further trials, FREEDOM and FREEDOM2, are in progress to understand long-term effects of fedratinib; and include strategies to mitigate gastrointestinal toxicity, monitor thiamine levels and surveil for encephalopathy. We use fedratinib for symptomatic MF following ruxolitinib failure in patients without significant cytopenias; with practical strategies for monitoring and managing potential toxicity.

• Authors: James T England, Vikas Gupta
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 23 Issue 15 Pg. 1677-1686 (Oct 2022) ISSN: 1744-7666 [Electronic] England
• PMID: 36252265 (Publication Type: Review, Journal Article)

Chemical References

• ruxolitinib
• fedratinib
• Janus Kinase Inhibitors
• Janus Kinase 2
• Nitriles
• Protein Kinase Inhibitors

Topics

• Humans
• Primary Myelofibrosis (drug therapy, diagnosis)
• Janus Kinase Inhibitors (adverse effects)
• Janus Kinase 2
• Nitriles (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)