Bempedoic acid is a convenient, complementary, cost-effective, first-in-class, orally available, once-daily LDL-C lowering drug that significantly reduces elevated LDL-C levels in patients with hypercholesterolemia, including patients inadequately treated with current lipid-modifying therapies. Bempedoic acid, a novel, non-statin, targeted therapy, works solely in the liver to block cholesterol biosynthesis. It enters the liver through a mechanism distinct from those that selectively take up statins.
Once in the liver, bempedoic acid is converted to a coenzyme A (CoA) derivative, or ETC-1002-CoA, which directly inhibits ATP citrate lyase (ACL), a key enzyme that supplies substrate for cholesterol and fatty acid synthesis in the liver. Inhibition of ACL by ETC-1002-CoA results in reduced cholesterol synthesis and upregulation of LDL receptor activity in the liver. This promotes the removal of LDL-C from the blood.
To date, Esperion has studied bempedoic acid in eighteen completed Phase 1 and Phase 2 clinical studies, and is currently evaluating bempedoic acid in four global pivotal Phase 3 LDL-C lowering efficacy and safety studies and one cardiovascular outcomes trial.
Bempedoic Acid Phase 2 Completed Clinical Studies**
|Study Number||Short Title (N=total/ETC-1002 treated)||LDL-C Lowering* (pbo corrected)||Dose Range (mg)||Treatment Duration|
|003||Phase 2a in Patients with Hypercholesterolemia (N=177/133)||Up to 27% (25%)||40, 80, 120||12 Wks|
|005||Phase 2a in Patients with Hypercholesterolemia and Type 2 Diabetes (N=60/30)||43% (39%)||80, 120||4 Wks|
|006||Phase 2a in Patients with Hypercholesterolemia and a History of Statin Intolerance (N=56/37)||32% (29%)||60, 120,
|007||Phase 2a in Patients with Hypercholesterolemia Added-on to Atorvastatin 10 mg (N=58/42)||22% (22%)||60, 120, 180, 240||8 Wks|
|008||Phase 2a in Patients with Hypercholesterolemia with or without Intolerance vs. Ezetimibe (N=349/249)||Up to 30% (1002)
Up to 48% (1002 + ezetimibe)
120 + ezetimibe, 180 + ezetimibe
|009||Phase 2b in Patients with Hypercholesterolemia while on Stable Statin Therapy (N=134/88)||24% (20%)||120, 180||12 Wks|
|014||Phase 2a in Patients with Hypercholesterolemia and Hypertension (N=143/72)||21% (24%)||180||6 Wks|
|035||Phase 2 in Patients with Hypercholesterolemia Added-on to High-Dose Statin (N=68/45)||13% (22%)||180||4 Wks|
Total Subjects: 1045 / Treated: 810
*Average LDL-C % change from baseline (placebo corrected)
**As of October 2016
Phase 2 Clinical Study Results
Our completed Phase 2 clinical studies have demonstrated significant LDL-C reductions of up to 30% as monotherapy, almost 50% in combination with ezetimibe, and an incremental 20%+ on top of any statin at any dose. Bempedoic acid also consistently lowers high sensitivity C-reactive protein, or hsCRP, an important marker of the underlying inflammation associated with cardiovascular disease.
Across eighteen completed clinical studies, bempedoic acid has displayed consistent and compelling, positive clinical results.
Initially, we intend to seek approval of bempedoic acid in the U.S. and Europe for patients with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) with elevated levels of LDL-C not adequately controlled with current lipid-modifying therapies. Some patients with elevated LDL-C are only able to tolerate less than the lowest approved daily starting dose of a statin and can be considered “statin intolerant”. We are confident patients, physicians, and payers will welcome a convenient, complementary, cost-effective, once-daily, oral LDL-C lowering therapy, especially the estimated 8 million patients in the U.S., Europe and Japan who are considered “statin intolerant,” a population with a high level of unmet medical need. In Europe, we are also seeking approval for use of bempedoic acid in “statin intolerant” patients with elevated LDL-C.