A pharmacological profile of pacritinib for the treatment of myelofibrosis.

INTRODUCTION

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, progressive cytopenias, and limited overall survival. While Janus kinase (JAK) inhibitors have transformed symptom- and spleen-directed management, many patients, particularly those with baseline thrombocytopenia, historically had limited therapeutic options due to treatment-related myelosuppression and exclusion from pivotal trials. Pacritinib was developed to address this unmet need through selective JAK2, ACVR1, and IRAK1 inhibition with relative sparing of JAK1.

AREAS COVERED: This review summarizes the pharmacologic properties, preclinical rationale, and clinical development of pacritinib for the treatment of MF. We discuss early-phase studies, pivotal phase III trials, dose-optimization efforts, and post-approval real-world data, with particular emphasis on patients with severe thrombocytopenia.

EXPERT OPINION: Pacritinib occupies a distinct niche within the MF treatment landscape, offering meaningful spleen and symptom benefit in patients with severe thrombocytopenia who historically lacked effective therapeutic options. While no JAK inhibitor has demonstrated clear disease-modifying effects in MF, pacritinib's non-myelosuppressive profile, unique activity against IRAK1, and potential anemia benefit via ACVR1 inhibition suggests potential utility as a backbone for future combination strategies. Ongoing and future studies will be critical to further define its role in phenotype-driven MF management.