A Case Study of Model-Informed Drug Development of a Novel PCSK9 Antisense Oligonucleotide. Part 2: Phase 2 to Phase 3.

ABSTRACT: In this second part of a case study on the practical use of model-informed drug development (MIDD), we describe the clinical development of AZD8233, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) antisense oligonucleotide, from phase 2b to the start of phase 3. The case study exemplifies the use of MIDD to answer key design questions for the phase 3 program, including the design of a pivotal phase 3 study, a head-to-head study, and a cardiovascular outcome study informed by model-averaging analysis. Extensive phase 3 study simulations assessed the impact of drop-out, readout timing, dose frequency, and analysis method on study outcomes. The final phase 3 design assumed around 1% monthly drop-out (based on other PCSK9 inhibitor trials), used an EMA/FDA-approved analysis metho

SUBMITTER: Knochel J 

PROVIDER: S-EPMC12521069 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature