Abstract 18: Bempedoic Acid Lowers Low Density Lipoprotein-Cholesterol and Attenuates Aortic Atherosclerosis in LDL Receptor-Deficient (LDLR+/- and LDLR-/-) Yucatan Miniature Pigs

Bempedoic acid (ETC-1002) is an oral investigational drug that targets hepatic adenosine triphosphate-citrate lyase to reduce cholesterol biosynthesis. In Phase 2 studies (up to 12 weeks in duration), bempedoic acid lowers elevated LDL-cholesterol (C) in patients with hypercholesterolemia. The objective of the present study was to test the ability of bempedoic acid to decrease plasma-C and LDL-C, and attenuate the development of atherosclerosis in a large animal model of familial hypercholesterolemia. Gene targeting has been used to generate Yucatan miniature pigs heterozygous (LDLR+/-) or homozygous (LDLR-/-) for LDL-receptor (R) deficiency (ExeGen). LDLR+/- pigs (n=12) and LDLR-/- pigs (n=12) were fed a high fat, cholesterol-containing diet (34% kcal fat; 0.2% cholesterol) and orally administered placebo or bempedoic acid at 120 mg/d and at 240 mg/d for 160 days. Bempedoic acid was well tolerated; weight gain, caloric intake, liver enzymes and clinical chemistry analyses were unaffected by treatment. In...