General AML|IDH1/2

The FDA grants enasidenib priority review for treatment of R/R AML with IDH2 mutation

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.

  1. Fierce Biotech: Celgene, Agios gain FDA speedy review for AML med enasidenib. 2017 Mar 1. [Accessed 2017 Mar 2].
  2. Yen K. et al. AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations. Cancer Discov. 2017 Feb 13. DOI: 1158/2159-8290.CD-16-1034. [Epub ahead of print].