Ivosidenib (Tibsovo)

General information

Class/mechanism: IDH1 inhibitor. Ivosidenib inhibits the mutant isocitrate dehydrogenase 1 (IDH1) enzyme at lower drug concentrations than wild-type IDH1. Inhibiting mutant IDH1 enzyme prevents formation of the oncometabolite 2-hydroxyglutarate (2HG) in leukemia cells, causes a reduction in IDH1-expressing tumor cells, and increases percentages of mature myeloid cells.

Diseases for which it is established

• IDH1-mutated AML
• Cholangiocarcinoma

Patient drug information

• Ivosidenib (Tibsovo) package insert
• Ivosidenib (Tibsovo) patient drug information (Chemocare)

History of changes in FDA indication

Acute myeloid leukemia

• 2018-07-20: Granted approval for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. (Based on [https://clinicaltrials.gov/ct2/show/NCT02074839 Clinical Trial Registry AG120-C-001])
• 2019-05-02: FDA approval expanded for newly-diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation, as detected by an FDA-approved test, in patients who are at least 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. (approval expanded to first-line setting with limitations; based on [https://clinicaltrials.gov/ct2/show/NCT02074839 Clinical Trial Registry AG120-C-001])
• 2022-05-25: Approved in combination with azacitidine for newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation, as detected by an FDA-approved test in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. (Based on AGILE)

Cholangiocarcinoma

• 2021-08-25: Approved for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation. (Based on ClarIDHy)

Also known as

• Code name: AG-120
• Brand name: Tibsovo