Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance

BackgroundOnce-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin intolerant patients.ObjectivesTo study the efficacy and safety of ETC-1002 (a novel LDL-C–lowering agent) in patients with hypercholesterolemia and a history of statin intolerance.MethodsPatients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C.ResultsETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, −35.4 to −22.1; P < .0001). ETC-1002 significantly reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal (P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002–treated patients.ConclusionsETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects

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

BackgroundETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia.ObjectivesTo 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).MethodsThis 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.ResultsEZE 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.ConclusionsIn 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)