Model-Informed Paradigm in Drug Development-An End-To-End Case Study From Upadacitinib Development

Area of Science:

• Pharmacometrics
• Quantitative Pharmacology
• Drug Development Science

Background:

• Model-informed drug development (MIDD) utilizes quantitative methods to enhance drug development decision-making.
• MIDD is crucial for improving efficiency amidst rising costs and competition in the pharmaceutical industry.
• Upadacitinib is an orally administered selective Janus kinase inhibitor approved for multiple inflammatory conditions.

Purpose of the Study:

• To describe a unique case of successful MIDD application throughout the upadacitinib development program.
• To present the applications and impact of modeling and simulation in informing key development decisions for upadacitinib.
• To offer a framework for other drug development programs based on lessons learned from upadacitinib.

Main Methods:

• Application of quantitative modeling and simulation approaches.
• Integration of MIDD from Phase 1 clinical trials through post-approval stages.
• Analysis of decision-making processes informed by MIDD in the upadacitinib program.

Main Results:

• Demonstrated successful application of MIDD across the entire upadacitinib development lifecycle.
• MIDD approaches informed critical decisions including dose optimization and clinical trial design.
• Successful regulatory approvals for upadacitinib in various indications were supported by MIDD.

Conclusions:

• The upadacitinib program exemplifies the successful integration and impact of MIDD.
• MIDD provides a valuable framework for efficient and effective drug development.
• Lessons learned from upadacitinib can guide future drug development strategies using MIDD.