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.
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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)
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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
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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)
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