About INCB018424
INCB018424: A JAK1/JAK2 inhibitor1
INCB018424 is a selective oral JAK1/JAK2 inhibitor that has no significant activity against a panel of 26 non-JAK kinases when tested at a concentration more than 80 times higher than the IC50 for JAK2.1 As a dual JAK1/JAK2 inhibitor, this agent has the potential to modulate two important kinases that may play a role in myeloproliferative neoplasms (MPNs), including primary myelofibrosis (MF).2
In preclinical studies, INCB018424 reduces the pro-inflammatory cytokine cascades mediated by JAK1, as well as inhibits hematopoiesis outside the bone marrow mediated by JAK2. Both of these pathways are believed to be implicated in MPN progression.1,3 It has been suggested that INCB018424 has an effect regardless of JAK2 mutation status: therefore, the presence of a JAK2V617F mutation may not be necessary for this agent to be active.2
Early clinical studies suggest that INCB018424 may decrease splenomegaly, reduce inflammatory cytokines, and improve symptoms in patients with MF.2 In Phase I/II studies INCB018424 was well tolerated, with thrombocytopenia as the only dose limiting toxicity. However, thrombocytopenia was reversible and manageable with a dose reduction in most patients. Other adverse events were mild to moderate and include diarrhea (5.9%), nausea (2.0%), headache (3.3%), and dizziness (2.6%).1