Ivosidenib: First Global Approval

Drugs. 2018 Sep;78(14):1509-1516. doi: 10.1007/s40265-018-0978-3.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Approval
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic
  • Glycine / administration & dosage
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Glycine / therapeutic use
  • Humans
  • Isocitrate Dehydrogenase / antagonists & inhibitors*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / pharmacology*
  • Pyridines / therapeutic use

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyridines
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Cytochrome P-450 CYP3A
  • ivosidenib
  • Glycine