Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance

• Published in: Journal of clinical lipidology Vol. 10; no. 3; pp. 556 - 567
• Main Authors: Thompson, Paul D., MacDougall, Diane E., Newton, Roger S., Margulies, Janice R., Hanselman, Jeffrey C., Orloff, David G., McKenney, James M., Ballantyne, Christie M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2016
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular; Cholesterol, LDL - blood; ETC-1002; Ezetimibe; Ezetimibe - pharmacology; Ezetimibe - therapeutic use; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Male; Middle Aged; Muscles - drug effects; Myalgia; Safety; Statin intolerance; Statin-associated muscle symptoms; Young Adult; ETC-1002; Statin-associated muscle symptoms; Hypercholesterolemia; Myalgia; Ezetimibe; Statin intolerance
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2015.12.025

ETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia. To compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg (EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C). This phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE. EZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P < .0001 vs EZE), respectively. The combination of ETC-1002, 120 mg or 180 mg plus EZE reduced LDL-C by 43% and 48%, respectively (both P < .0001 vs EZE). ETC-1002 alone or combined with EZE also reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, LDL particle number, and high-sensitivity C-reactive protein compared with EZE alone. Across all treatment groups, statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups. In patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836). •ETC-1002, alone and combined with ezetimibe, was studied for cholesterol reduction.•ETC-1002 monotherapy reduced LDL-C up to 30% and combination therapy up to 48%.•ETC-1002 reduced LDL-C similarly in statin-intolerant and statin-tolerant patients.•ETC-1002 reduced LDL-C, non–HDL-C, apolipoprotein B, and CRP more than ezetimibe.•Rates of muscle-related adverse events were similar in all treatment groups.