Abstract 16127: Effect of REGN727/SAR236553 Anti-Proprotein Convertase Subtilisin/Kexin Type 9 Fully Human Monoclonal Antibody in Patients with Elevated Triglycerides/Low High-Density Lipoprotein Cholesterol: Data from Three Phase 2 Studies (NCT:01266876; 01288469; 01288443)

Abstract

Background: Low-density lipoprotein cholesterol (LDL-C) is regarded as the primary target for risk reduction in hypercholesterolemia. However, patients with associated high triglycerides (TGs) and low high-density lipoprotein cholesterol (HDL-C) levels may be at enhanced risk for CVD. REGN727/SAR236553 (SAR236553) a PCSK9 fully human monoclonal antibody (mAb) has recently completed phase 2 clinical trials and demonstrated reductions in LDL-C of up to 72%. The goal of this analysis was to determine if SAR236553 maintained similar reductions in LDL-C in patients with low HDL-C or elevated TGs at baseline, as well as to determine the effect of SAR236553 on HDL-C, TGs and other lipid parameters in these subsets of patients.

Methods: SAR236553 was studied in three add-on, double-blind, randomized, placebo-controlled phase 2 studies consisting of 352 hypercholesterolemic patients including FH (heterozygous familial hypercholesterolemia [HeFH]) and non-FH patients, 77 on placebo and 275 on doses of SAR236553, ranging from 50 to 300 mg, administered SC either Q2W or Q4W. Of these patients, 179 were treated with 150 mg Q2W or placebo and were the focus of this analysis. At baseline, 20% of patients had HDL ≤ 40 mg/dL and 36% had TGs >150 mg/dL. All participants were on background lipid-lowering therapies, which consisted of a statin or statin + ezetimibe 10 mg.

Results: In the subset of patients receiving SAR236553 150 mg Q2W with baseline low HDL-C and/or elevated TGs the reductions in LS-mean LDL-C were 69.1% (± 4.0%) and 72.4% (± 3.0%), respectively. These reductions were similar to those seen in the entire 150 mg Q2W cohort in which LS-mean LDL-C ranged from 66.2 to 72.4%, with a pooled effect of 68.4%. Similar effects were observed for non-HDL-C, apoB, and Lp(a). There were trends for greater increases in HDL-C in patients with low HDL-C at baseline and for greater reductions in TGs in patients with elevated TG levels at baseline. The most common adverse event was mild injection-site reactions of short duration.

Conclusions: These results indicate that SAR236553 provided similar robust LDL-C reductions in patients with varying forms of dyslipidemia at baseline, additional analysis in larger populations are needed to confirm these results.