帕克替尼 (Vonjo)

概览

Pacritinib is a kinase inhibitor used for the treatment of primary and secondary myelofibrosis in adult patients with significantly reduced platelet counts.

作用机制

While the pathogenesis of myelofibrosis (MF) is still poorly understood, both primary and secondary (i.e. post-polycythemia vera or post-essential thrombocythemia) myelofibrosis have been associated with mutations of JAK2. Signaling pathways initiated by JAK2 generate a number of cytokines and growth factors responsible for hematopoiesis and immune functioning, and its dysregulation is thought to be a driver of MF pathogenesis. Pacritinib is thought to exert its pharmacologic activity via inhibition of wild-type JAK2, mutant JAK2, and FMS-like tyrosine kinase 3 (FLT3). It has a greater inhibitory potency towards JAK2 than related proteins (e.g. JAK3, TYK2), and does not inhibit JAK1 at clinically relevant concentrations. Pacritinib also exhibits some inhibitory activity against other cellular kinases (e.g. CSF1R and IRAK1), although the clinical significance of this activity is unknown.

适应症

Pacritinib is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 x 10/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

• High-Risk Secondary Myelofibrosis
• High risk Primary Myelofibrosis (PMF)
• Intermediate risk Primary Myelofibrosis (PMF)
• Intermediate risk Secondary Myelofibrosis