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.

Keywords:

• Janus kinase inhibitors
• myelofibrosis
• myeloproliferative disease
• pacritinib
• ruxolitinib
• treatment

Declaration of interest

DP McLornan received speaker fees and research support from Novartis. C Harrison was the co-chief investigator for PERSIST-I and chief investigator for COMFORT-II. She has received support for research from Novartis, is on the advisory board for Novartis, CTI Biopharma, Baxter, Gilead and Sanofi and has also received speaker fees from Sanofi, Novartis and CTI Biopharma. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.