Bempedoic Acid
Bempedoic Acid: A Novel Agent
Bempedoic acid has been designed as an oral, once-daily therapy that has significantly reduced low-density lipoprotein cholesterol (LDL-C) levels when added to other lipid-lowering therapies in clinical trials of patients with primary hyperlipidemia who need additional LDL-C lowering.1
 
Designed to Have a First-in-Class Mechanism of Action
Bempedoic acid is an oral, nonstatin therapy designed to primarily work in the liver to inhibit cholesterol biosynthesis.2  

Bempedoic acid is a prodrug that is complementary to—yet distinct from—other lipid-lowering therapies, including statins.2

Bempedoic acid is converted to its active moiety primarily in the liver, and inhibits adenosine triphosphate citrate lyase (ACL)—an enzyme two steps upstream from HMG-CoA reductase, the target of statins—along the cholesterol biosynthesis pathway.2

Bempedoic acid is converted to its active moiety by very long-chain acyl-CoA synthetase-1 (ACSVL1), which is not present in skeletal muscle.2

By inhibiting ACL, bempedoic acid is designed to reduce cholesterol synthesis, resulting in LDL receptor upregulation.2

Bempedoic Acid Mechanism of Action
Adapted from Pinkosky et al.

Development Timeline for Bempedoic Acid1,3-7
Bempedoic Acid
Oral, small molecule
 
Lowering
elevated LDL-C
PHASE 1
PHASE 2
PHASE 3
NDA filed
Feb. 20, 2019
MAA filed
Feb. 11, 2019
CVD
risk reduction

Cardiovascular Outcomes Trial ongoing
 
 
In tandem with a New Drug Application (NDA) submission for bempedoic acid, Esperion submitted an NDA for an LDL-C lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet through the abbreviated 505(b)(2) pathway on February 20, 2019.  

Also, on February 11, 2019, Esperion submitted a Marketing Authorization Application (MAA) for an LDL-C lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet consistent with the European Medicines Agency’s “Guideline on Clinical Development of Fixed Combination Medicinal Products.”

5 Phase 3 trials ~4000 patients

Get updates about ESPERION and bempedoic acid
References: 1. Data on file. Esperion Therapeutics, Inc. 2019. 2. Pinkosky SL, Newton RS, Day EA, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016;7:13457. doi:10.1038/ncomms13457. 3. Evaluation of major cardiovascular events in patients with, or at high risk for, cardiovascular disease who are statin intolerant treated with bempedoic acid (ETC-1002) or placebo (CLEAR Outcomes). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02993406. Accessed February 8, 2019. 4. Evaluation of long-term safety and tolerability of ETC-1002 in high-risk patients with hyperlipidemia and high CV risk (CLEAR Harmony). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02666664. Accessed February 8, 2019. 5. Evaluation of the efficacy and safety of bempedoic acid (ETC-1002) in patients with hyperlipidemia and statin intolerant (CLEAR Serenity). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02988115. Accessed February 8, 2019. 6. Evaluation of the efficacy and safety of bempedoic acid (ETC-1002) as add-on to ezetimibe therapy in patients with elevated LDL-C (CLEAR Tranquility). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03001076. Accessed February 8, 2019. 7. Evaluation of long-term efficacy of bempedoic acid (ETC-1002) in patients with hyperlipidemia at high cardiovascular risk (CLEAR Wisdom). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT0299111. Accessed February 8, 2019.