Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia

Future Oncol. 2018 Apr;14(9):797-807. doi: 10.2217/fon-2017-0494. Epub 2017 Dec 13.

Abstract

The treatment landscape for myelofibrosis (MF) has reached the molecular era by targeting different pathways that are implied in this myeloproliferative neoplasm. A few years ago, the first-in-class JAK1/JAK2 inhibitor ruxolitinib, demonstrated reductions in both constitutional symptoms and splenomegaly, leading to the US FDA approval. The development or worsening of cytopenias in patients receiving ruxolitinib uncovered an unmet need that has been addressed by alternative approaches. Pacritinib, a dual JAK2 and FLT3 inhibitor which also inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated splenomegaly and symptom burden, while having limited myelosuppression with manageable gastrointestinal toxicity. Herein, we provide an overview of pacritinib, from early preclinical studies to the latest and ongoing PAC203 trial, as an emerging therapy for MF.

Keywords: FLT3 inhibitors; JAK inhibitors; myelofibrosis; myeloproliferative neoplasms; pacritinib.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Bridged-Ring Compounds / administration & dosage*
  • Bridged-Ring Compounds / adverse effects
  • Female
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / antagonists & inhibitors
  • Janus Kinase 2 / antagonists & inhibitors
  • Male
  • Primary Myelofibrosis / complications
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / pathology
  • Protein Kinase Inhibitors / administration & dosage*
  • Pyrazoles / therapeutic use
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Splenomegaly / complications
  • Splenomegaly / drug therapy
  • Splenomegaly / pathology
  • Thrombocytopenia / complications
  • Thrombocytopenia / drug therapy*
  • Thrombocytopenia / pathology
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors

Substances

  • 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
  • INCB018424
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • JAK2 protein, human
  • Janus Kinase 2
  • IRAK1 protein, human
  • Interleukin-1 Receptor-Associated Kinases