Dr. Verstovsek on the Mechanism of Action of Momelotinib in Myelofibrosis

Srdan Verstovsek, MD, PhD, professor, director, Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses the mechanisms of action of momelotinib in myelofibrosis.

Momelotinib inhibits JAK1 and JAK2, as well as the ALK2 protein, which is the receptor on the surface of hepatocytes and other radical endothelial systems, such as the lining the GI tract or the spleen, Verstovsek says. Inhibiting ALK2 reduced the levels of hepcidin, which are high in the blood of patients with myelofibrosis and are related to the degree of anemia and overall survival, Verstovsek adds.

Through the inhibition of ALK2, momelotinib appears to improve the red blood cell (RBC) count and anemia, allowing patients to become transfusion independent, Verstovsek continues. Improving RBC counts is something that sets momelotinib apart from other JAK inhibitors, Verstovsek concludes.