Ivosidenib: First Global Approval.

Ivosidenib (Tibsovo) is a small molecule, orally available inhibitor of mutated cytosolic isocitrate dehydrogenase 1 (IDH1) that is being developed by Agios Pharmaceuticals for the treatment of cancer in patients with IDH1 mutations. The mutated form of the IDH1 enzyme produces a metabolite, 2-hydroxyglutarate (2-HG), which is thought to play a role in the formation and progression of acute myeloid leukaemia (AML), gliomas and other cancers. Elevated 2-HG levels interfere with cellular metabolism and epigenetic regulation, thereby contributing to oncogenesis. Ivosidenib targets the IDH1 metabolic pathway to prevent a build-up of the oncometabolite 2-HG. This article summarizes the milestones in the development of ivosidenib leading to this first approval in the USA for the treatment of patients with relapsed or refractory AML with a susceptible IDH1 mutation. Clinical development for AML, cholangiocarcinoma, glioma, myelodysplastic syndromes and solid tumours is ongoing worldwide.