Izicopan Shows No CYP3A4 Inhibition at >100 µM, No Time-Dependent DDIs
A Ki-based TDI study shows izicopan does not inhibit CYP3A4 (IC₅₀ > 100 µM) and exhibits no time-dependent inhibition in midazolam and testosterone assays. These data support izicopan’s low risk of drug–drug interactions and liver toxicity, reinforcing its differentiated profile as a best-in-class C5aR inhibitor.
1. Ki-Based TDI Study Results
InflaRx conducted a Ki/Kinact time-dependent inhibition study demonstrating that izicopan exhibits no CYP3A4 inhibition up to 100 µM, with an IC₅₀ exceeding 100 µM and no shift in inhibition potency. Using midazolam and testosterone probe substrates, the study confirmed absence of time-dependent inhibition, indicating minimal risk of CYP3A4-mediated drug–drug interactions.
2. Implications for Clinical Development
The mechanistic confirmation of no CYP3A4 inhibition supports izicopan’s favorable safety and pharmacological profile, reducing concerns about hepatotoxicity and metabolic interactions. This low DDI risk enhances its potential as a best-in-class oral C5aR inhibitor and facilitates combination regimens in ongoing and future inflammatory disease trials.