AG-221, first-in-class IDH2 mutation inhibitor shows promise

Cancer metabolism represents an important emerging field regarding novel tumour targeting. Mutations in the isocitrate dehydrogenase 2 (IDH2) enzyme confer a novel gain-of-function in cancer cells that results in the accumulation and secretion of a metabolite that alters cell differentiation. In an ongoing phase I trial of AG-221—a first-in-class inhibitor of mutated IDH2—in patients with relapsed or refractory acute myeloid leukaemia or myelodysplastic syndrome, the drug was shown to be well tolerated with no dose-limiting toxic effects and good clinical activity, even at the lowest dose tested. So far, 7 out of 10 patients have had a complete remission, indicating IDH2 is a promising therapeutic target.