Comparative quantitative systems pharmacology modeling of anti-PCSK9 therapeutic modalities in hypercholesterolemia

Viсtor Sokolov et al.

J Lipid Res. 2019 Sep; 60(9): 1610–1621.

•The challenge: PCSK9 inhibition therapies are an actively expanding field in hypercholesterolemia treatment, as a substitute or an add-on therapy in dyslipidemic patients. Multiple PCSK9 compounds are already on the market or are currently being developed, thereby creating a strong competition environment.

•Thus, understanding the differences and assessing potential advantages of various anti-PCSK9 modalities in different patient populations under wide range of doses and regimens becomes critical on early stages of development.

• The achievement: Through collaboration of M&S Decisions and AstraZeneca, a QSP model was developed to describe lipoprotein metabolism. This allowed to evaluate the effects of various anti-PCSK9 treatments on major dyslipidemia biomarkers, to quantify the differences between treatment modalities, and to understand the impact of background statin treatment on anti-PCSK9 efficacy.

Quantitative Systems Pharmacology modeling helps understand the differentiation potential of PCSK9 siRNA in relation to key competitors

Please, see a more detailed presentation (Sokolov_PCSK9.pdf) and a full text article (J Lipid Res (2019) 60, 1610-1621_Sokolov)