Physiologically based pharmacokinetic (PBPK) modeling and simulation has become an established approach to assess drug-drug interaction (DDI) liabilities involving CYP enzymes, with transporters and/or absorption-related mechanisms evolving in its acceptance by regulators. In addition, the use of PBPK modeling in specific populations such as organ impairment populations has been recently highly encouraged by the US FDA.
Successful application of PBPK models during regulatory review can be used in lieu of clinical trials and to inform drug product label. In the recent NDA submission of asciminib (Scemblix©) by Novartis, PBPK simulations replaced over 10 clinical pharmacology studies and played an instrumental role in the approval of two additional doses by the US FDA with no additional clinical pharmacology studies at the date of approval.
This webinar provides an overview of the development and verification of the asciminib PBPK model as well as its applications focusing on highlights from the regulatory review and the impact on the drug product label.