Targeting Mutated Isocitric Dehydrogenase 1 (mIDH 1) in Acute Myeloid Leukemia (AML): Story of Ivosidenib

Abstract

In 2008, mutations in isocitric dehydrogenase 1 & 2 (mIDH 1 & 2) was first detected in glioblastoma multiforme (GBM) from among many types of solid tumour. The next year i.e. in 2009 acute myelogenous leukemia (AML) showed the presence of such mutation. mIDH 2 blocker enasidenib came into the market for the first time for adult recurrent and relapsed AML in 2017. But mIDH 1 blocker ivosidenib (AG-120) is approved in 2019 in recurrent and relapsed AML. At the end of 2019, it was approved for untreated adult AML. When it was in the early phase trial it became eligible for a special expanded access program as it showed encouraging results. The drug molecule’s progress through preclinical and regulatory path is interesting. It is worthwhile to investigate how it received market authorization while the phase III trial was not over. Trial of both GBM and AML started in March 2014. Circumstances behind ivosidenib being first approved in adult recurrent and relapsed AML rather than in glioma where the mutation was first found are also discussed.