Nexletol From Esperion Therapeutics, Inc

The FDA has approved Nexletol (bempedoic acid), a nonstatin cholesterol-lowering agent, in adults who require additional lowering of low-density lipoprotein cholesterol (LDL-C).

It is indicated for patients with established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia as an adjunct to dietary modifications and in conjunction with maximally tolerated statin therapy. The approval carries the limitation that the effect of Nexletol on cardiovascular morbidity and mortality has not been determined.¹ About 15 million Americans are unable to achieve guideline-recommended LDL-C levels, even during treatment with statin medications. Nexletol is the first nonstatin, once-daily, oral, LDL-C—lowering medication to receive FDA approval since 2002.²

PHARMACOLOGY AND PHARMACOKINETICS

Nexletol is an adenosine triphosphate-citrate lyase (ACL) inhibitor. ACL inhibition leads to decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors.

Nexletol achieves steady-state plasma concentrations after 7 days of oral administration and displays linear pharmacokinetics. Its mean elimination half-life is about 21 hours. The pharmacokinetics of Nexletol are not affected by age, gender, race, or weight.¹

DOSAGE AND ADMINISTRATION

The dose of Nexletol is 180 mg orally once daily, with or without food. Lipid levels should be checked within 8 to 12 weeks of starting treatment. No dosage adjustment is required in patients with mild or moderate renal impairment. There are limited data regarding the use of Nexletol in patients with severe renal impairment, and it has not been studied in patients with end-stage renal disease who are receiving dialysis. Nexletol does not require a dose adjustment in patients with mild or moderate hepatic impairment. It has not been studied in patients with severe hepatic impairment.¹

CLINICAL TRIALS

The efficacy of Nexletol was evaluated in 2 double-blind, multicenter, placebo-controlled, randomized trials of adults with established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were taking maximally tolerated statin therapy. Both studies lasted 52 weeks, with efficacy evaluated at week 12. Study 1 consisted of 2230 participants, and study 2 consisted of 779 participants. The primary efficacy outcome measure of each study was the percent change from baseline to week 12 in LDL-C. As compared with a placebo, the LDL-C of the Nexletol group decreased by 18% in study 1 and by 17% in study 2. Maximum LDL-C—lowering effects were demonstrated in both studies at week 4.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

There are no contraindications to treatment with Nexletol.

Nexletol inhibits renal tubular organic anion transporter 2 and may increase blood uric acid levels, which may lead to the development of gout. In clinical trials, uric acid elevation usually occurred within the first 4 weeks of initiation of therapy and continued throughout treatment. Serum uric acid should be assessed when clinically appropriate. Patients should contact their health care providers if symptoms of hyperuricemia occur, and providers should monitor patients for signs and symptoms of hyperuricemia, using urate-lowering drugs when warranted. Nexletol is associated with an increased risk of tendon injury or rupture, which may occur within weeks to months of initiation of therapy. Tendon rupture may occur more frequently in individuals who are older than 60 years, are taking corticosteroid or fluoroquinolone drugs, have renal failure, or with previous tendon disorders. Treatment discontinuation should be considered in patients who experience joint inflammation, pain, or swelling. Should a tendon rupture occur, Nexletol should be discontinued immediately. The use of Nexletol should be avoided in patients with a history of tendon disorders or rupture.

Nexletol should not be used concomitantly with more than 20 mg of simvastatin or more than 40 mg of pravastatin. It should not be used during breastfeeding or pregnancy.

The most common adverse reactions are abdominal discomfort or pain, anemia, back pain, bronchitis, elevated liver enzymes, hyperuricemia, muscle spasms, pain in extremity, and upper respiratory tract infection.¹

REFERENCES

• Nexletol. Prescribing Information. Esperion Therapeutics, Inc; 2020. Accessed June 12, 2020. https://pi.esperion.com/nexletol/nexletol-pi.pdf.
• Esperion announces FDA approval of Nexletol (bempedoic acid) tablet, an oral, once-daily, non-statin LDL-cholesterol lowering medicine [news release]. Ann Arbor, MI; Feb. 21, 2020: Esperion Therapeutics, Inc. https://www.esperion.com/investors-media/press-releases/ Accessed March 29, 2020.