Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2 and IRAK1 developed for the treatment of patients with myeloproliferative diseases including myelofibrosis. Unlike other JAK2 inhibitors pacritinib does not inhibit JAK1. Inhibition of JAK1 has been associated with immune dysfunction, lymphomas and may also worsen thrombocytopenia and anemia. Pre-clinical data demonstrate that inhibition of IRAK1 reduces inflammation, which along with the function of JAK2, is a key component of MF. Pacritinib’s unique MOA (JAK2/IRAK1) may allow for reductions of both splenomegaly and constitutional systems and may reduce the risk of cytopenias and immune dysfunction associated with other JAK inhibitors.
Pacritinib has been studied in over 1,200 patients including the completed Phase 3 PERSIST clinical trial program in myelofibrosis. These studies demonstrated clinical responses for reduction of spleen volume and symptom improvement for patients with all platelet counts including severe thrombocytopenia.