Novel agent safely and effectively reduces LDL-c, also in statin-intolerant hypercholesterolaemia patients

ETC-1002 Lowers LDL-C More than Ezetimibe in Patients with Hypercholesterolemia with or without Statin Intolerance

News - Mar. 16, 2015

Presented during the ACC Scientific Session in a moderated poster session and via a webcast


ETC-1002 is a unique, first-in-class, orally available, once-daily small molecule (bempedoic acid) designed to lower LDL-cholesterol levels and avoid the side effects associated with therapies currently available for lowering LDL-cholesterol. ETC-1002 has a unique dual mechanism of action that has the potential to regulate both lipid and carbohydrate metabolism. ETC-1002 appears to work by inhibiting ATP citrate lyase (ACL), a key enzyme in the cholesterol biosynthetic pathway, and activating a complementary enzyme, 5′-adenosine monophosphate-activated protein kinase (AMPK). Both enzymes are known to play significant roles in the synthesis of cholesterol and glucose in the liver. By inhibiting cholesterol synthesis in the liver, ETC-1002 causes the liver to take up LDL particles from the blood, which reduces LDL-C levels.
The results of the randomized, double-blind, active comparator-controlled, parallel group, multicenter phase 2b ETC-1002-008 clinical study were presented, in patients with (n=177) or without (n=171) statin intolerance. Doses of ETC-1002 120 and 180 mg, with or without ezetimibe 10 mg treatment, were compared. Secondary objectives also included to assess the effect of ETC-1002 on additional lipid and cardiometabolic biomarkers; characterize the safety, tolerability and rates of muscle-related adverse events; and assess lipid-lowering efficacy in combination with ezetimibe versus ezetimibe monotherapy.

Main results

  • All tested doses of ETC-1002 yielded significantly larger reductions of LDL-c from baseline as compared with ezetimibe alone, with the highest reductions obtained in combination with ezetimibe (up to 48% reduction in week 12). ETC-1002 monotherapy yielded LDL-c reductions of up to 30% from baseline, as compared with ezetimibe monotherapy.
  • The LDL-c lowering effect of ETC-1002 with or without ezetimibe was similar in statin intolerant and statin tolerant patients.
  • ETC-1002 therapy alone or in combination with ezetimibe also beneficially affected other lipid and cardiometabolic biomarkers to a larger extent than did ezetimibe alone.
  • Serious adverse events (AEs) were very rare. The frequency of drug-related AEs were similar in all treatment groups, except for a higher event rate in patients treated with ETC-1002 180 mg + ezetimibe 10 mg.
    Muscle-related AEs were similar in all treatment groups, but more often seen in patients with a history of statin intolerance.
    No significant changes in body weight or glucose or blood pressure were observed.


This study shows that in patients with hypercholesterolaemia, including those with statin intolerance, ETC-1002 is a potential new therapy to effectively lower LDL-c, more so than does ezetimibe. Treatment with ETC-1002 is safe and has a similar tolerability profile to ezetimibe. Combination therapy with ezetimibe merits further investigation.

- This article was written based on a webcast of a conference call, which was released on the Esperion website -

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