The data demonstrated that omacetaxine reduced the number of leukemic stem cells in the bone marrow by more than 80% in an animal model of CML (mice with BCR-ABL-induced CML disease). In contrast, the tyrosine kinase inhibitor imatinib mesylate (Gleevec) did not reduce the number of leukemic stem cells in the bone marrow. Consistent with the killing of CML stem cells, omacetaxine provided a significant survival benefit to mice with two different types of leukemia; BCR-ABL-induced CML and B cell acute lymphoblastic leukemia (B-ALL).
The study also demonstrated that omacetaxine inhibited cell proliferation and markedly reduced the expression of the anti-apoptotic protein Mcl-1 in leukemic cell lines. Mcl-1 is a key target protein in several types of leukemias and other cancers, and is believed to be one of the major targets through which omacetaxine causes clinical responses.
Greg Collier, managing director and CEO of ChemGenex, said: “These data suggest the potential of omacetaxine to be utilized across a range of leukemias, and support clinical application beyond CML, as well as the potential to extend disease-free survival in this disease.”