On 1st March 2017, the U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) and granted priority review to enasidenib for the treatment of Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) with an Isocitrate Dehydrogenase 2 (IDH2) mutation.1
Somatic gain of function mutations in IDH2 are observed in patients with AML. IDH2 mutations can lead to the accumulation of the oncometabolite 2-Hydroxyglutarate (2-HG). 2-HG can inhibit TET2, which can lead to epigenetic dysregulation and a block in cellular differentiation. Enasidenib (AG221) is a reversible, selective inhibitor of mutated IDH2. Enasidenib binds and inhibits the mutant IDH2 enzyme that is responsible for the accumulation of 2-HG.2
At present, enasidenib is being explored in a phase III (NCT02577406) randomized study. In this study, the safety and efficacy of enasidenib is compared to conventional care regimens in older AML patients that are R/R after second or third-line AML therapy and are positive for IDH2 mutation. The primary endpoint of the study is overall survival.