Next-Generation JAK Inhibitors in the Treatment of Myeloproliferative Neoplasms Available to Purchase

JAK inhibitors have changed the treatment landscape of myeloproliferative neoplasms, graft-versus host and several autoimmune conditions. While approved JAK inhibitors generally target the JAK2 kinase domain, and several also the JAK1 kinase domain in active form (type I inhibition), new inhibitors have progressed to clinical trials that either exhibit a type II mechanism of inhibition of the kinase domain in an inactive state or that target the pseudokinase domain with potential preference or specificity for the JAK2 V617F mutant. This is the most prevalent mutant in myeloproliferative neoplasms. An ideal inhibitor would target persistently activated JAK2 in MPNs, eradicate the clone or induce deep molecular remission in addition to clinical and hematological remission and spare wild type JAK2 that is critical for hematopoiesis and immune response. We discuss perspectives of these and other modes of JAK inhibition and primary as well as secondary/exploratory study endpoints in clinical trials design, along with potential biomarker correlates to evaluate potential efficacy of the next generation versus conventional JAK inhibitors.