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The first drug to block a mutant metabolic enzyme in cancer. With azacitidine it tripled survival in IDH1-mutated AML that could not take intensive chemotherapy.
Approved 2018 (relapsed/refractory IDH1 AML), 2019 (newly diagnosed unfit, monotherapy), 2022 (with azacitidine, AGILE: EFS HR 0.33, OS 24.0 vs 7.9 months, HR 0.44), 2021 (IDH1 cholangiocarcinoma), and 2023 (IDH1 MDS). Servier acquired the Agios oncology portfolio in 2021. Differentiation syndrome is the class toxicity; isocitrate-dehydrogenase-2 isoform switching and second-site IDH1 mutations cause resistance.
Allosteric inhibitor of mutant IDH1; blocks 2-hydroxyglutarate production, restoring TET2-dependent demethylation and differentiation. Connects to IDH1 / IDH2.
1.Mutant IDH1 converts α-ketoglutarate to the oncometabolite 2-HG
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance: how tumours escape each drug class · Lines of therapy.
Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026).
Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy. IDH1 mutation by an approved test.
Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
Sources: NICE TA948. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
First IDH1 inhibitor
Combination with azacitidine (AGILE)
| Region | Year | Indication |
|---|---|---|
| US | 2018 | Relapsed/refractory IDH1-mutated AML |
| US | 2019 | Newly diagnosed IDH1-mutated AML unfit for intensive chemotherapy |
| US | 2021 | Previously treated IDH1-mutated cholangiocarcinoma |
| US | 2022 | Newly diagnosed IDH1-mutated AML with azacitidine (AGILE) |
| US | 2023 | Relapsed/refractory IDH1-mutated MDS |
| UK | 2024 | Locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation after one or more systemic treatments; NICE TA948 recommended 31 January 2024 with a commercial arrangement · https://www.nice.org.uk/guidance/ta948 |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Differentiation syndrome AGILE combination arm | 14% | - |
| QT prolongation | 20% | - |
| Neutropenia with azacitidine | - | 27% |
| Leukocytosis | 12% | - |
Rates read from the US prescribing information. Blank cells mean the figure was not sourced, not that it is zero.
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AGILE showed that for the roughly 6-10% of AML patients with an IDH1 mutation, a targeted doublet produces survival in the range of two years, an outcome previously unimaginable in unfit patients. Ivosidenib-azacitidine is approved and is one option alongside venetoclax-azacitidine for these patients. Which regimen, or triplet, is best for IDH1-mutated disease has not been settled by a randomised trial.
IDH1 testing at diagnosis and relapse now directs patients to a targeted oral drug; ivosidenib went on to be combined with azacitidine in newly diagnosed disease (AGILE).
Query for this drug: (TITLE:"Ivosidenib" OR ABSTRACT:"Ivosidenib" OR TITLE:"Tibsovo" OR ABSTRACT:"Tibsovo") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Ivosidenib, not a curated reading list.
Shares Mutant IDH / 2-hydroxyglutarate, Differentiation syndrome, IDH1 R132 mutation, IDH inhibitors.
Shares Mutant IDH / 2-hydroxyglutarate, Differentiation syndrome, IDH inhibitors, Beat AML Master Trial.
Shares Mutant IDH / 2-hydroxyglutarate, IDH1 R132 mutation, IDH inhibitors, Glutamine addiction.
Shares IDH1- and IDH2-mutated acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Higher-risk myelodysplastic syndromes, Acute myeloid leukaemia in older or unfit patients.
Shares AGILE, AGILE: ivosidenib plus azacitidine for newly diagnosed IDH1-mutated AML in patients unfit for intensive chemotherapy, IDH1 / IDH2, Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome.
Shares Mutant IDH / 2-hydroxyglutarate, IDH inhibitors, Servier, IDH1 / IDH2.
Shares Glutamine addiction, Metabolic theory of cancer: from Warburg to oncometabolites, Cancer metabolism, Hallmarks of cancer as a synthesis of the theories.
Shares Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer, SAFIR-ABC10, Intrahepatic cholangiocarcinoma, Biliary tract cancer (all types).