Bempedoic acid is a convenient, complementary, consistent, once-daily, oral 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 first-in-class, non-statin, targeted therapy, works in the liver to block cholesterol biosynthesis.
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 completed Phase 1 and Phase 2 clinical studies conducted in approximately 1,300 patients and treated over 800 patients with bempedoic acid. The Company is currently evaluating bempedoic acid in four, fully enrolled global pivotal Phase 3 LDL-C lowering efficacy and safety studies consisting of approximately 3,600 patients, a Phase 3 open-label extension study and the CLEAR Outcomes global cardiovascular outcomes trial (CVOT).
Bempedoic Acid Phase 2 Clinical Studies**
|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|
|038||Phase 2 in Patients with Hypercholesterolemia Added-on to
Ezetimibe & Atorvastatin 20 mg (N=63/43)
|64% (61%)||180||6 Wks|
|039||Phase 2 in Patients with Hypercholesterolemia Added-on to Evolocumab 420 mg (N=52/26)||Study Ongoing||180||8 Wks|
Total Subjects: 1,160 / Treated: 765
*Average LDL-C % change from baseline (placebo corrected)
**As of October 2017
Phase 2 Clinical Study Results
Our completed Phase 2 clinical studies of bempedoic acid have demonstrated significant LDL-C reductions of up to 30% as monotherapy, almost 50% with the bempedoic acid / ezetimibe combination pill, 64% in the bempedoic acid / ezetimibe combination with 20 mg of atorvastatin and an incremental 20%+ on top of statins, including high-intensity statins. Bempedoic acid also consistently lowers high sensitivity C-reactive protein, or hsCRP, an important marker of the underlying inflammation associated with cardiovascular disease.
With approximately 1,300 patients studied and over 800 patients treated, the bempedoic acid-based franchise of products have displayed consistent and compelling, positive clinical results.
Esperion plans to submit a New Drug Application (NDA) by the first quarter of 2019 for an LDL-C lowering indication for bempeodic acid based on the successful completion of the Company’s ongoing and fully-enrolled global pivotal Phase 3 program. The proposed product label would include specific language for use of bempedoic acid as an adjunct to maximally tolerated statin therapy in patients with hypercholesterolemia, specifically those at high cardiovascular disease (CVD) risk with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) who require additional LDL-C lowering. In Europe, we intend to submit a Marketing Authorization Application (MAA) in the first quarter of 2019 for the use of bempedoic acid in combination with a statin, or statin with other lipid-lowering therapies, in patients unable to reach LDL-C lowering goals with maximally tolerated statin therapy and in patients who are statin intolerant, or for whom as statin is contraindicated.
We are confident patients, physicians, and payers will welcome additional convenient, complementary, consistent, once-daily, oral LDL-C lowering therapies in the U.S. and Europe.