Fedratinib hydrochloride to treat intermediate-2 or high-risk primary or secondary myelofibrosis.

Abstract

Fedratinib hydrochloride is a selective Janus kinase 2 (JAK2) inhibitor approved by the U.S. Food and Drug Administration (FDA) in August 2019 for intermediate- 2 or high-risk primary or secondary myelofibrosis. The approval of this novel oral agent was based on the phase II and III JAKARTA-2 and JAKARTA trials, which both showed significant reduction in splenomegaly and myelofibrosis symptom burden. The most common adverse effects associated with fedratinib include anemia, gastrointestinal symptoms and elevation in liver transaminases. Early clinical trial data was concerning for an increased incidence of Wernicke's encephalopathy (WE), which led the FDA to place a clinical hold on further drug development. However, upon further investigation it was determined that there was no clear evidence that fedratinib causes WE, and the clinical hold was lifted in 2017. This inclusive review provides insight into the pharmacology, safety and efficacy, and future direction of fedratinib use in myeloproliferative neoplasms.

• Authors: M Schiffer, A Kowalski, J Zhao, J P Bewersdorf, R S Lewis Jr, A M Zeidan
• Journal: Drugs of today (Barcelona, Spain : 1998) (Drugs Today (Barc)) Vol. 56 Issue 12 Pg. 755-768 (Dec 2020) ISSN: 1699-3993 [Print] Spain
• PMID: 33332482 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright 2020 Clarivate Analytics.

Chemical References

• Protein Kinase Inhibitors
• Pyrrolidines
• Sulfonamides
• fedratinib

Topics

• Drug Development
• Humans
• Primary Myelofibrosis (drug therapy)
• Protein Kinase Inhibitors (adverse effects)
• Pyrrolidines
• Sulfonamides