Abstract 16196: Impact of Baseline PCSK9 Levels on the Efficacy of Evolocumab, a Monoclonal Antibody Against PCSK9
Introduction: Evolocumab (AMG 145), a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), significantly reduces low-density lipoprotein-cholesterol (LDL-C) by ~65%. Whether baseline PCSK9 levels impact the efficacy of evolocumab remains undefined.
Methods: The mean placebo-controlled percent change from baseline in LDL-C measured by ultracentrifugation at week 10 & 12 was calculated for evolocumab 140 mg Q2W and 420 mg QM in 2293 patients from the pooled phase 3 trials. Median PCSK9 levels were measured in 138 patients from a substudy of the pooled phase 2 trials. For both analyses, patients were stratified into quartiles based upon baseline PCSK9 levels. Interaction tests were performed to evaluate for heterogeneity across quartiles.
Results: At baseline in the pooled phase 3 trials, the median PCSK9 level was 323 ng/mL (25th %ile 258 ng/mL; 75th %ile 406 ng/mL). Demographics were similar across quartiles of baseline PCSK9, but, as expected, patients with higher levels of baseline PCSK9 were more likely to be receiving more intensive background statin therapy and had lower levels of LDL-C at baseline. Evolocumab 140 mg Q2W reduced PCSK9 levels by >90% 1 week after dosing and levels remained low (~100 ng/mL), regardless of baseline PCSK9 level (Figure top left). Evolocumab 420 mg QM rendered PCSK9 levels undetectable 1 week after dosing and reduced by >90% 2 weeks after dosing, regardless of baseline PCSK9 levels (Figure top right); 3 weeks after dosing PCSK9 levels remained low (~100 ng/mL) and by 4 weeks levels remained proportionately reduced by nearly half. Evolocumab significantly (P<0.001) reduced LDL-C at week 10 and 12 and to a similar extent regardless of baseline PCSK9 (Figure bottom).
Conclusion: Evolocumab, a PCSK9 inhibitor, when administered 140 mg biweekly or 420 mg monthly, consistently and substantially reduces PCSK9 and LDL-C regardless of a patient’s baseline level of PCSK9.
Author Disclosures: N. Desai: None. R. Giugliano: Honoraria; Modest; Daiichi Sankyo, Merck. Consultant/Advisory Board; Modest; Amgen Inc., Daiichi Sankyo, Merck, Janssen. Research Grant; Significant; Amgen, Daiichi Sankyo, Merck. S. Wasserman: Employment; Significant; Employee of Amgen Inc, received Amgen stock. J. Gibbs: Employment; Significant; Employee of Amgen, Inc, received Amgen stock. T. Liu: Employment; Significant; Employee of Amgen, Inc, received Amgen stock. R. Scott: Employment; Significant; Employee of Amgen, Inc, received Amgen stock. M. Sabatine: Research Grant; Significant; Amgen, AstraZeneca, Bristol Myers Squibb, Sanofi Aventis, Daiichi Sankyo, Eisai, Genzyme, GlaxoSmithKline, Intarcia, Merck, Takeda. Honoraria; Modest; Aegerion, Amgen, Astra Zeneca, Bristol Myers Squibb, Sanofi Aventis, Daiichi Sankyo, Eisai, Genzyme, GlaxoSmithKline, Intarcia, Merck, Pfizer, Vertex.
- © 2014 by American Heart Association, Inc.