Bempedoic acid, sold under the brand name Nexletol among others, is a medication for the treatment of hypercholesterolemia. Bempedoic acid blocks an enzyme in the liver called adenosine triphosphate citrate lyase, which is involved in making cholesterol. Bempedoic acid was approved for use in the United States in February 2020, and for use in the European Union in April 2020.
Medical uses
In the US, bempedoic acid is indicated for the treatment of hypercholesterolemia in combination with diet and the highest tolerated statin therapy in adults with heterozygousfamilial hypercholesterolemia, or with established atherosclerotic cardiovascular disease, who need additional lowering of LDL cholesterol. In the EU, bempedoic acid is indicated in adults with primary hypercholesterolaemia or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL C goals with the maximum tolerated dose of a statin; or alone or in combination with other lipid-lowering therapies in patients who are statin intolerant, or for whom a statin is contraindicated.
Bempedoic acid does not interact with the cytochrome P450 enzyme system in the liver and only weakly inhibits the transporter proteins SLCO1B1, SLCO1B3 and SLC22A7. Despite this, the drug increases blood levels of statins. The effect is most pronounced with simvastatin and pravastatin, whose AUC is increased about twofold. No other clinically relevant interactions have been found in studies.
Following oral intake, bempedoic acid reaches highest blood plasma concentrations after 3.5 hours. Food does not affect its absorption. When in the bloodstream, 99.3% of the substance are bound to plasma proteins. About a fifth of the substance is reversibly converted by an aldo-keto reductase enzyme to a metabolite that is also pharmacologically active in form of its coenzyme A–thioester. Of ESP15228, 99.2% are bound to plasma proteins. Both bempedoic acid and the metabolite are inactivated by glucuronidation of their carboxylic acid groups. Bempedoic acid has a biological half-life of 21±11 hours. Over 95% of the substance are excreted in form of metabolites; about 70% with the urine and 30% with the feces.
History
In a study, it reduced LDL cholesterol by about 20 mg/dl compared to placebo and had no more side effects than placebo, although a higher percentage of drug receiving subjects dropped out of the study because of side effects., its effects on cardiovascular morbidity and mortality have not been determined; but studies are under way. In January 2020, the Committee for Medicinal Products for Human Use in the European Union recommended granting of a marketing authorization for bempedoic acid as both a standalone drug and as a combination drug with ezetimibe. Bempedoic acid was approved for use in the European Union in April 2020. In February 2020, bempedoic acid was approved for use in the United States. The U.S. Food and Drug Administration granted the approval of Nexletol to Esperion Therapeutics. The FDA approved bempedoic acid based on evidence from two clinical trials of 3009 subjects with high LDL cholesterol and known atheroscleroticcardiovascular disease or HeFH. The trials were conducted in United States, Canada, and Europe. There were two clinical trials that evaluated the benefits and side effects of bempedoic acid. The trial designs were similar. All enrolled subjects were on a low cholesterol diet and taking the highest dose of a statin, for high cholesterol. In both trials, subjects were randomly assigned to receive bempedoic acid or placebo tablets every day for 52-weeks. Neither the subjects nor the health care providers knew which treatment was being given. The trials measured percent change in LDL-C blood levels from baseline to week 12 and compared bempedoic acid to placebo.
