Assessment of Pharmacokinetic Drug Interaction of Asciminib with Atorvastatin in Healthy Participants

Asciminib is the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP) in patients with chronic myeloid leukemia. This phase 1, two-treatment-period, drug-drug interaction study evaluated the effect of steady-state asciminib on the pharmacokinetics of atorvastatin. A single dose of atorvastatin (20 mg) was administered on day 1 (period 1: days 1-4). On days 5-11 (period 2: days 5-12), 80 mg asciminib was administered once daily, with a single dose of atorvastatin co-administered on day 9. Pharmacokinetic sampling for atorvastatin was performed on days 1-4 in period 1 and days 9-12 in period 2. Twenty-two healthy participants were enrolled. Twenty participants completed the study, and two discontinued due to adverse events (AEs). Asciminib increased the adjusted geometric mean (G_mean) of maximum plasma concentration (C_max), the area under the curve (AUC) from zero to the last quantifiable concentration (AUC_last), and the AUC from zero to infinity (AUC_inf) of atorvastatin by 24%, 16%, and 14%, respectively, and did not affect these parameters for its active metabolites, o-hydroxy-atorvastatin and p-hydroxy-atorvastatin. Plasma concentrations of coproporphyrin-1 (CP-1), an endogenous substrate of the atorvastatin transporter OATP1B, were not affected by asciminib. Thirteen participants reported at least one AE, all being grade 1/2, except for one grade 3 AE (increased alanine aminotransferase). No serious AEs were reported. In conclusion, concomitant administration of steady-state asciminib and atorvastatin resulted in a small, clinically irrelevant increase in atorvastatin exposure and no change in CP-1 concentrations. Both drugs were well tolerated. These data support co-administration of asciminib and atorvastatin.