PACRITINIB

12.1 Mechanism of Action Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, FMS-like tyrosine kinase 3 (FLT3), and interleukin 1 receptor associated kinase-1 (IRAK1) which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Pacritinib is also an inhibitor of activin A receptor, type 1/activin receptor like-kinase 2 (ACVR1/ALK2). MF is often associated with dysregulated JAK2 signaling. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib has higher inhibitory activity for JAK2 compared to JAK3 and tyrosine kinase 2 (TYK2). Pacritinib exhibits inhibitory activity against additional cellular kinases, such as colony stimulating factor 1 receptor (CSF1R), of which the clinical relevance in myelofibrosis is unknown.

Contraindications

• • 4 CONTRAINDICATIONS VONJO is contraindicated in patients concomitantly using strong CYP3A4 inhibitors or inducers as these medications can significantly alter exposure to pacritinib
• • which may increase the risk of adverse reactions or impair efficacy [see Warnings and Precautions ( 5.1
• • 5.2
• • 5.3
• • 5.4 )