Case Study: Alexion Pharmaceuticals advances mRNA lipid nanoparticle development with Certara QSP modeling

Quantitative systems pharmacology model of mRNA lipid nanoparticle for two programs at the preclinical to clinical transition

Alexion Pharmaceuticals, a biopharmaceutical company, faced the challenge of developing a therapy for Crigler-Najjar syndrome type 1 using an mRNA lipid nanoparticle (LNP) platform. The in vivo mechanism of action and clinical pharmacology for their candidate were unknown, creating a significant hurdle for translating preclinical findings into first-in-human clinical studies. They collaborated with Certara (via its Applied BioMath division, which it acquired) to leverage their Quantitative Systems Pharmacology (QSP) consulting services.

Certara developed a mechanistic QSP model based on first principles to understand the therapy's mechanisms and guide clinical design. The model successfully predicted outcomes that matched both single and multi-dose rat data. For Alexion, this solution helped guide candidate selection, optimize and reduce the number of preclinical studies, justify the elimination of some biomarkers, inform the recommended safe starting dose, and project the consequences of non-linear parameters for the first-in-human dose, thereby de-risking the transition to clinical trials.

Alexion Pharmaceuticals