Bempedoic Acid

Breast Feeding; Lactation; Milk, Human; Anticholesteremic Agents; Hypolipidemic Agents; Enzyme Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Danger

H302 (33.3%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P264, P264+P265, P270, P280, P301+P317, P305+P351+P338, P318, P319, P330, P337+P317, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Bempedoic acid is associated with low rate of mild, asymptomatic and typically transient serum aminotransferase elevations during therapy. In prelicensure controlled trials, elevations in either ALT or AST arose in 2% of treated patients compared to less than 1% of placebo recipients. ALT elevations above 3 times the upper limit of normal (ULN) arise in less than 1% of bempedoic treated patients, a rate similar to that in placebo recipients (most of the participants were taking other cholesterol lowering agents such as statins or ezetimibe). There were no instances of serum ALT elevations associated with symptoms or jaundice in the prelicensure trials. Since the approval and more widespread use of bempedoic acid, there have been no published reports of clinically apparent liver injury attributed to its use.

C - Cardiovascular system

QC - Cardiovascular system

Bempedoic acid inhibits the synthesis of cholesterol in the liver, reducing LDL-C levels. This reduces the development of atherosclerotic plaques that may increase the risk of cardiovascular events. Earlier clinical trials studying the effects of bempedoic acid showed a dose‐dependent reduction of LDL‐C levels in addition to decreased LDL particle number, and reduced levels of apolipoprotein B, non–HDL cholesterol, and high‐sensitivity C‐reactive protein. Due to its unique mechanism of action, bempedoic acid is not associated with myositis, an adverse effect that frequently accompanies statin therapy. More recent trials have supported that this drug significantly decreases LDL-C levels after 12 weeks of therapy and provides additional lowering of LDL-C when combined with ezetimibe and statin therapy. The effects of bempedoic acid on mortality are currently unknown.

Normally, LDL cholesterol is produced in the liver and circulates in the blood. When the blood becomes saturated, excess LDL deposits in blood vessels including the coronary arteries, increasing the risk of cardiovascular events. Bempedoic acid is a prodrug that requires activation in the liver. The very-long-chain acyl-CoA synthetase-1 (ACSVL1) enzyme is responsible for its activation to ETC-1002-CoA, the pharmacologically active metabolite. ATP lyase (also known as ATP synthase) plays an important part of cholesterol synthesis. BETC-1002-CoA directly inhibits this enzyme after the parent drug is activated in the liver by coenzyme A (CoA). This inhibition leads to upregulation of the LDL cholesterol receptor, reducing serum LDL-C via increased uptake and LDL clearance in the liver. By the above mechanisms, bempedoic acid causes a total decrease of circulating LDL-C that normally damages blood vessels and leads to atherosclerosis. Lastly, ETC-1002 activates AMP-activated protein kinase (AMPK) in rodents, which inhibits the synthesis of cholesterol via the inhibition of HMG-CoA reductase. The relevance of this to humans is unknown.