Nexletol From Esperion

The FDA has approved broad new label expansions for bempedoic acid (Nexletol; Esperion Therapeutics, Inc) to reduce the risk of myocardial infarction and coronary revascularization in adults with established cardiovascular disease (CVD) or a high risk for a CVD event who are unable to use statin therapy. The medication is also approved as an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)–lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia.¹

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PHARMACOLOGY AND PHARMACOKINETICS

Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor. In the cholesterol biosynthesis pathway, ACL is an enzyme upstream of 3-hydroxy-3-methylglutarylcoenzyme A reductase. The inhibition of ACL decreases cholesterol synthesis in the liver, resulting in lower LDL-C. Bempedoic acid reaches maximum concentration 3.5 hours after administration, achieves steady state after 7 days, and has an elimination half-life of approximately 21 hours. Its pharmacokinetics are not affected by age, gender, race, or weight.¹

The recommended dose of bempedoic acid is 180 mg administered orally once daily, taken with or without food. Lipid levels should be checked within 8 to 12 weeks of beginning treatment.¹

CLINICAL TRIALS

The expanded indications for bempedoic acid were based on data from the CLEAR Outcomes trial (NCT02993406), a double-blind, event-driven, placebo-controlled, randomized trial of 13,970 adults with either established CVD or a high risk for a CVD event but without diagnosed CVD who were not receiving recommended statin dosages. Participants were randomly assigned 1:1 to receive bempedoic acid 180 mg per day or placebo either alone or in addition to other background lipid-lowering therapies. Participants were followed until the end of the trial or death, with a median follow-up duration of 3.4 years.

The primary composite end point was major adverse cardiovascular events (MACE-4; time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization), and the key secondary composite end point was MACE-3 (time to first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke).

Both end points were significantly reduced in participants taking bempedoic acid compared with those taking placebo. The group receiving bempedoic acid also demonstrated a 20% decrease in LDL-C from baseline to month 6.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment is contraindicated in patients with a history of a serious hypersensitivity reaction to bempedoic acid or any of its components.

Because elevations in serum uric acid have occurred, uric acid levels should be monitored periodically, along with signs and symptoms of hyperuricemia, and treatment with urate-lowering drugs should be initiated if required. The use of bempedoic acid is associated with an increased risk of tendon injury or rupture. Its use should be avoided in patients with a history of tendon disorders or rupture, and the drug should be discontinued at the first sign of tendon rupture. Discontinuation of the medication should be considered if joint inflammation, pain, or swelling occurs, and patients should be advised to rest and seek medical care at the first sign of tendonitis or tendon rupture. Bempedoic acid should not be used concomitantly with simvastatin doses greater than 20 mg or pravastatin doses greater than 40 mg. The medication should not be used during pregnancy or breastfeeding.

The most common adverse reactions in the primary hyperlipidemia trials were abdominal pain or discomfort, anemia, back pain, bronchitis, elevated liver enzymes, hyperuricemia, muscle spasms, pain in extremity, and upper respiratory tract infection. The most common adverse reactions in the cardiovascular outcomes trial were anemia, cholelithiasis, elevated liver enzymes, gout, hyperuricemia, muscle spasms, and renal impairment.¹

REFERENCES

1. Nexletol. Prescribing information. Esperion Therapeutics Inc; 2024. Accessed June 19, 2024. https://pi.esperion.com/nexletol/nexletol-pi.pdf

2. US FDA approves broad new labels for Nexletol and Nexlizet to prevent heart attacks and cardiovascular procedures in both primary and secondary prevention patients, regardless of statin use. News release. Esperion Therapeutics. March 22, 2024. Accessed June 19, 2024.https://www.esperion.com/news-releases/news-release-details/us-fdaapproves-broad-new-labels-nexletolr-and-nexlizetr-prevent