Physiologically Based Pharmacokinetic Modeling and Simulations in Lieu of Clinical Pharmacology Studies to Support the New Drug Application of Asciminib.

ABSTRACT: Background: Asciminib (Scemblix^®) is approved for the first-line treatment of adult patients with chronic myeloid leukemia in the chronic phase at 40 mg twice daily (BID) and 80 mg once daily (QD) or 200 mg BID for patients harboring the T315I mutation. Objectives: (1) Extrapolate the DDI magnitude as the perpetrator or victim of other drugs and the effect of organ impairment to untested doses; (2) Predict clinically untested DDI scenarios. Methods: Asciminib is primarily cleared by cytochrome P450 (CYP)3A4, UDP-glucuronosyltransferases (UGT)2B7, UGT2B17, UGT1A3/4, and the breast-cancer-resistance protein (BCRP). In vitro asciminib is an inhibitor of several CYP, UGT enzymes, and transporters and is an inducer of CYP1A2 and CYP3A4. Clinical DDI studies asses

SUBMITTER: Loisios-Konstantinidis I 

PROVIDER: S-EPMC12567041 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature