N. Kaila, E. Wang, K. Sweeney, D. Plowchalk; Pfizer Inc., Groton, CT

BACKGROUND: Monoclonal antibodies (mAbs) against PCSK9 produce robust reductions of LDL-C and therefore may reduce cardiovascular risk in patients. To better understand the clinical efficacy of anti-PCSK9 mAbs as a therapeutic class and the important covariates of response, we have conducted a model-based meta-analysis of available data for bococizumab, evolocumab and alirocumab.
METHODS: Placebo-corrected % change from baseline (%CFB) LDL-C for three anti-PCSK9 mAbs from 30 studies and 118 treatment arms were included in the analysis. The maximal LDL-C effect (Emax) and individual potencies (ED50) of each mAb were modeled and the covariate effect of background statins was estimated. Exploratory analyses of secondary lipid biomarkers were also conducted.
RESULTS: The model fitted dose-response relationship between mAb dose and LDL-C % CFB is shown below, plotted in the presence or absence of background statin therapy. Marked pharmacological responses were also observed for total cholesterol, non-HDL-C, triglycerides, HDL-C, ApoB, ApoA1, Lp(a) and VLDL-C.
CONCLUSION: The combined analysis of study-level data indicates, as a class, the maximal mean LDL-C %CFB (95% CI) for anti-PCSK9 mAbs at nadir is -77% (-83%, -71%) in the presence of background statins. In the absence of statins the Emax was reduced to -64% (-68 %, -60%).