DDI Regulatory Poster Child using the Simcyp Simulator: Ibrutinib (Imbruvica®)
Pharmacylics and J&J sought to bring ibrutinib, its new tyrosine kinase inhibitor therapy targeting rare B-cell malignancies to market. The company leveraged FDA’s accelerated approval program; it was one of the first to be awarded breakthrough status by the agency. Ibrutinib is susceptible to interactions with a strong inhibitor and inducer of CYP3A4 enzymes, thus posing potential drug-drug interactions (DDI). Additionally, a dose optimization approach was needed to adjust the regimen for cancer populations.
The simulations of PBPK model provided a dose optimization strategy for combined use of ibrutinib with specific CYP3A inhibitors or inducers.