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
• IDH1-mutated MDS
• 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 AG120-C-001 r/r)
• 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 AG120-C-001 untreated)
• 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)

Myelodysplastic syndrome (MDS)

• 2023-10-24: Approved for adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation. (Based on AG120-C-001 r/r)

History of changes in EMA indication

• 2023-05-04: Tibsovo in combination with azacitidine is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy.
• 2023-05-04: Tibsovo monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy.

Also known as

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