PII-022 - ADVERSE DRUG EVENT RISK ASSESSMENT BY THE VIRTUAL ADDITION ON THE NEW GLYT1 INHIBITOR (BI 425809) TO THE ACTUAL DRUG REGIMEN OF A LARGE COHORT OF PATIENTS
Thursday, March 28, 2024
5:00 PM – 6:30 PM MDT
S. Haertter1, P. Dow2, M. Smith3, V. Michaud4,5,6, R. Bikmetov7, J. Turgeon2, M. Desch8, G. Condon9, L. Condon3, L. Bentzel3; 1Translational Med & Clin Pharmacology, Boehringer-Ingelheim, Boehringer Ingelheim Pharma GmbH & Co KG - Ingelheim, Rheinland-Pfalz, Germany, 2Galenus RX Inc, 3Tabula Rasa Health Care Inc., 4GalensuRX Inc., Orlando, FL, USA, 5Faculty of Pharmacy, University of Montreal, Montreal, Qc, Canada, 6Centre de Recherche du CHUM (CRCHUM), Montreal, Qc, Canada, 7Ilumed LLC, 8Boehringer-Ingelheim GmbH & Co KG, 9GalenusRX Inc.
Background: Drug safety studies performed by biosimulations generate relevant information without exposing patients to adverse drug events (ADEs) Methods: In our study, the new Glyt1 inhibitor (BI-425809) was virtually added to patients’ actual drug regimen (N=4,405,063). Changes in risk level were estimated for risk of drug induced Long-QT syndrome and CYP450 drug interaction burden, based on pre-clinical data of BI 425809. Pharmacokinetic properties used were: Dose = 10 mg (oral); Bioavailability = 71%; Cmax = 222 nM; CYP3A4 weak affinity substrate (partial metabolic clearance about 80%); IC50 for hERG block = 30 M Results: A change in total medication risk score (MRS) was observed following addition of BI-425809 in ~50% (N=2,138,247) of the retained population: MRS increased from 6.3±6.6 to 7.2±6.6. Among patients with a change in MRS, ~65% had a 2-unit increase (max 11 units). The number of individuals classified as High/Severe MRS category increased by 3.1%. Addition of BI-425809 to patients receiving CYP3A4 perpetrator drugs produced a greater change in MRS (+1.5) vs patients not exposed to CYP3A4 perpetrators (+0.8). An additional 0,0032% of the population (n=139) would be at risk of QT prolongation following the addition of BI-425809. The model based on MRS changes predicted a $91 increase in medical expenditure (ED visits and hospitalizations) per patient ($3,172 to $3,263) following addition of BI-425809. Conclusion: This simulation strategy can help identify individuals at increased risk of ADEs. The increase in MRS was mostly driven by CYP3A4 interactions. Using this model, interactions can be identified a priori, making risk mitigable and preventable
