Pacritinib: a new agent for the management of myelofibrosis?

Abstract

INTRODUCTION:

Myelofibrosis (MF) is a clonal haematological disease associated with recurrent somatic gene mutations (JAK2V617F, MPL, CALR) and constitutive activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription pathway. MF is often characterised by debilitating symptoms and JAK inhibitors (JAKIs) have revolutionised available therapeutic options. Ruxolitinib, a JAK1 and 2 inhibitor, is the only currently approved agent. Several other JAKIs are undergoing evaluation in the clinical trial setting and Pacritinib , a novel JAK2 and FLT3 inhibitor, is at an advanced stage of investigation with recent completion of a Phase III trial and another ongoing.

AREAS COVERED:

Within this article we focus on pacritinib, summarising the development, preclinical and up-to-date results from the Phase I - III trials. We present the most recent data on efficacy and safety and indirectly compare this novel JAKI with ruxolitinib.

EXPERT OPINION:

The kinome array data for pacritinib suggests that it has a range of targets differing to those for ruxolitinib. Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients. It is also an attractive drug for potential combination studies due to its good tolerability.

• Authors: Yan Beauverd, Donal P McLornan, Claire N Harrison
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 16 Issue 15 Pg. 2381-90 ( 2015) ISSN: 1744-7666 [Electronic] England
• PMID: 26389774 (Publication Type: Journal Article, Review)

Chemical References

• 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene
• Bridged-Ring Compounds
• Nitriles
• Pyrazoles
• Pyrimidines
• ruxolitinib
• JAK1 protein, human
• JAK2 protein, human
• Janus Kinase 1
• Janus Kinase 2

Topics

• Bridged-Ring Compounds (therapeutic use)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Humans
• Janus Kinase 1 (antagonists & inhibitors)
• Janus Kinase 2 (antagonists & inhibitors)
• Nitriles
• Primary Myelofibrosis (drug therapy)
• Pyrazoles (therapeutic use)
• Pyrimidines (therapeutic use)
• Splenomegaly (drug therapy)