Evaluation of the pharmacokinetics of enasidenib in patients with hepatic impairment.

Yiming Cheng, Jian Chen, Carlos Vigil, Shahram Khanzadeh, Anita Rampersad, Thomas Prebet, Yan Li

Abstract readMulticenter Study

In one paragraph

Article in Cancer chemotherapy and pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Yiming ChengClinical Pharmacology, Pharmacometrics & Bioanalysis, Bristol Myers Squibb, Princeton, NJ, USA.

Jian ChenClinical Pharmacology, Pharmacometrics & Bioanalysis, Bristol Myers Squibb, Princeton, NJ, USA.

Carlos VigilHematology Global Drug Development, Bristol Myers Squibb, Giralda Farms, NJ, USA.

Shahram KhanzadehWorldWide Patient Safety, Bristol Myers Squibb, San Diego, CA, USA.

Anita RampersadHematology Clinical Science, Bristol Myers Squibb, Giralda Farms, NJ, USA.

Thomas PrebetEarly Clinical Development Hematology and Cell Therapy, Giralda Farms, NJ, USA.

Yan LiClinical Pharmacology, Pharmacometrics & Bioanalysis, Bristol Myers Squibb, Princeton, NJ, USA. Yan.Li@bms.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEnasidenib, an isocitrate dehydrogenase-2 (IDH2) inhibitor, is indicated for adult patients with relapsed/refractory acute myeloid leukemia (AML) with an IDH2 mutation. This study evaluated the pharmacokinetics (PK) and safety of enasidenib in subjects with hepatic impairment (HI).

methodsA multicenter, open-label study assessed the PK of a single 100 mg oral dose of enasidenib in subjects with mild (n = 8), moderate (n = 8), and severe (n = 8) HI (Child-Pugh classification) and matched healthy controls (n = 16). Plasma concentrations of enasidenib and its active metabolite, AGI-16,903, were analyzed, and PK parameters were compared between HI groups and healthy controls.

resultsFollowing a single oral dose, enasidenib exposure (AUC0-∞) was comparable across all groups, with geometric mean ratios (GMRs) of 97.7%, 96.7%, and 87.4% for mild, moderate, and severe HI versus healthy controls, respectively. Cmax values showed similar trends, with GMRs of 119%, 85.7%, and 86.4% for mild, moderate, and severe HI, respectively. AGI-16,903 exposure decreased with increasing HI severity, with GMRs for AUC0-∞ of 86.3%, 65.0%, and 61.1% for mild, moderate, and severe HI, respectively.

conclusionHI did not significantly alter PK of enasidenib. While AGI-16,903 exposure decreased with increasing HI severity, the impact was not deemed clinically relevant. Taken together, the results of this study support the conclusion that no dose adjustment is warranted for subjects with mild, moderate, or severe HI.

Indexed as

AminopyridinesAntineoplastic AgentsLiver DiseasesTriazinesAdministration, OralAdultAgedArea Under CurveFemaleHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteMaleMiddle AgedSeverity of Illness IndexAminopyridinesAntineoplastic AgentsenasidenibIDH2 protein, humanIsocitrate DehydrogenaseTriazinesEnasidenibHepatic impairmentPharmacokinetics

Identifiers

PMID40643669

DOI10.1056/NEJMoa1112304

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