Homogeneity of treatment effect of REGN727/SAR236553, a fully human monoclonal antibody against PCSK9, in lowering LDL-C: data from three phase 2 studies

Abstract

Purpose: REGN727/SAR236553 (REGN727), a fully human monoclonal antibody targeted to proprotein convertase subtilisin/kexin type 9 (PCSK9), has been evaluated as a treatment for hypercholesterolemia (HC) in three phase 2 studies. REGN727, added to different lipid-modifying therapies (LMT), resulted in significant reductions in LDL-C across the three studies. Mild injection site reaction was the most common treatment-emergent adverse event in treated patients (pts). To assess the consistency of treatment effect in lowering LDL-C in these studies, we analyzed homogeneity of effect across different subgroups. Methods: 352 pts with primary HC (familial or non-familial) and LDL-C ≥2.6 mmol/L on background LMT (including statin) were randomized in three double-blind, placebo-controlled phase 2 studies of 8- or 12-wk treatment duration; 77 pts were randomized to placebo and 275 pts to REGN727 (including 108 randomized to single 1 mL subcutaneous injections of 150 mg REGN727 every 2 wks [Q2W]). The 150 mg Q2W dose was further analyzed and data pooled for assessment. Obtained from an analysis of covariance, least squares (LS) mean percent change from baseline in LDL-C at wk 8/12 using last observation carried forward was assessed for subgroups by baseline age, gender, BMI, LDL-C, HDL-C, TG and statin dose. Results: LS mean (SE) % LDL-C reduction among 104 pts included in the analysis and receiving REGN727 150 mg Q2W was –68.4% (1.9) vs –10.5% (2.2) among 75 placebo pts included in the analysis. LS mean % LDL-C reductions for the various subgroups of pts receiving REGN727 150 mg Q2W are shown in the table. View this table: LS mean (SE) LDL-C reduction by subgroup Conclusions: In this subgroup analysis, REGN727 150 mg Q2W indicated homogeneity of treatment effect of REGN727 in lowering LDL-C across each of the factors studied. Nct: 01266876, 01288469,01288443