Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients

Abstract

Ezetimibe added to statin therapy further reduces LDL-C and clinical atherosclerotic cardiovascular disease compared to statin alone. However, the number of effective and safe oral agents for patients not at LDL-C goal is limited. In prior clinical trials, gemcabene reduced LDL-C and was generally well-tolerated in nearly 900 patients treated for up to 12weeks. To evaluate the LDL-C lowering and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. This was an 8-week, double-blind, placebo-controlled, randomized, phase 2 study in men and postmenopausal women ≥18 and ≤65 years of age with LDL-C ≥130mg/dL (3.4mmol/L) while on low-intensity to high-intensity stable statin (the majority on moderate intensity) therapy. Sixty-six patients were randomized 1:1:1 to gemcabene 300mg, 900mg, or placebo QD. Gemcabene 300mg and 900mg produced a mean percent change in LDL-C of -23.4±4.7% (P=.005) and -27.7 ±4.3% (P<.001), respectively, vs -6.2 ±4.3% for placebo. The median percent change in CRP was -26.1% (P=.196) and -53.9% (P<.001) for gemcabene 300mg and 900mg, respectively, vs -11.1% for placebo. Gemcabene 300mg and 900mg were well-tolerated with no significant difference in AEs compared to placebo. Gemcabene as add-on to stable statin therapy demonstrated additional dose-dependent and statistically significant reductions in LDL-C of >20% and CRP >40% compared to placebo. The results support gemcabene-continued development for patients requiring LDL-C lowering beyond that provided by background statin therapy.