Ivosidenib (Ivosenib) 250 mg, 60 tablets: profile, composition and research

Reference page for Ivosidenib (Ivosenib) 250 mg, 60 tablets. Active substance: Ивосидениб / Ivosidenib.

Key facts

What ivosidenib is

Ivosidenib is an oral medicine from the small-molecule inhibitor class. It is not used for tumours in general, only where the cell's genome carries a specific mutation in the IDH1 gene. That change has to be found in the laboratory first.

The substance is supplied as 250 mg tablets. The manufacturer states a daily dose of 500 mg, which is two tablets. A pack of 60 tablets covers roughly one month of continuous treatment.

This approach is called personalised oncology: the medicine is matched to the molecular profile of the tumour rather than to where in the body it sits.

How ivosidenib works

The mutant IDH1 enzyme

The IDH1 enzyme takes part in the Krebs cycle, the chain of reactions by which a cell obtains energy. Under a mutation, most often the R132H substitution, the enzyme changes behaviour: instead of its usual reaction it starts converting alpha-ketoglutarate into D-2-hydroxyglutarate.

Build-up of an oncometabolite

D-2-hydroxyglutarate accumulates in the cell and interferes with the enzymes that strip methyl marks from DNA and histones. As a result genes that govern the normal maturation of blood cells fall silent, and progenitor cells lose the ability to mature.

A return to maturation

Ivosidenib binds the mutant enzyme and lowers the production of D-2-hydroxyglutarate. Progenitor cells regain the ability to differentiate instead of dividing without control.

Why genetic testing comes first

Without a confirmed IDH1 mutation the medicine has no target. Molecular testing is therefore not a formality but a condition of prescription: it shows whether the tumour carries that particular target.

The test is run on a bone-marrow or blood sample. The result stays with the patient for the whole course of treatment, because it determines the very possibility of using the medicine.

Approved uses

The prescribing information names acute myeloid leukaemia with an IDH1 mutation in adults: both in newly diagnosed disease and in relapsed or refractory cases. The medicine is also used as part of combinations with other agents.

Prescribing, duration and monitoring of tolerability remain the task of a haematologist. Treatment may be accompanied by a specific complication, differentiation syndrome, so regular supervision and blood tests are required.

Published research

Primary sources, verified against PubMed:

• Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia., PubMed 35443108 (N Engl J Med, 2022).
• Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia., PubMed 31841594 (Blood, 2020).
• Multicenter Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for IDH1-Mutated Acute Myeloid Leukemia., PubMed 37014667 (Clin Cancer Res, 2023).
• Ivosidenib in acute myeloid leukemia., PubMed 37874005 (Expert Opin Pharmacother, 2023).

Listed for reference. Publication of a study is not a claim about this particular product.

Precautions

• This is a prescription medicine. Prescribing, dosing and monitoring belong to a haematologist.
• Use is possible only with a confirmed IDH1 mutation on molecular testing.
• Differentiation syndrome is possible, with fever, breathlessness, swelling and ECG changes. Such symptoms must be reported to a doctor at once.
• Treatment affects the blood, so monitoring tests are run. QT prolongation and other heart-rhythm changes are possible.
• In pregnancy the medicine can harm the fetus. Reliable contraception is needed during treatment and breastfeeding is stopped.
• Tell your doctor about every other medicine you take: interactions are possible, including with antifungal agents and herbal products.

Frequently asked