Treatment with bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor, reduces the risk of major adverse cardiovascular events (MACE) among statin-intolerant patients compared with placebo, according to phase 3 study data presented at the American College of Cardiology’s Annual Scientific Session & Expo together with the World Congress of Cardiology.
Bempedoic acid is currently marketed under the brand name Nexletol®, and in combination with ezetimibe, under the brand name Nexlizet®. Both Nexletol and Nexlizet are indicated as adjuncts to diet and maximally tolerated statin therapy, in patients with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular (CV) disease who require additional lowering of low-density lipoprotein cholesterol (LDL-C).
The randomized, double-blind, placebo-controlled phase 3 CLEAR Outcomes trial (ClinicalTrials.gov Identifier: NCT02993406) included 13,970 adult patients with or at high risk for CV disease with documented statin intolerance (inability to tolerate 2 or more statins, 1 at a low dose) and elevated LDL-C levels (fasting blood LDL-C ≥100 [2.6 mmol/L]).
Patients were randomly assigned 1:1 to receive either bempedoic acid 180mg orally once daily or placebo. The primary endpoint was the time to first occurrence of MACE, defined as CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.
Compared with placebo, the incidence of a primary endpoint event was found to be significantly lower with bempedoic acid (11.7% vs 13.3%; hazard ratio [HR], 0.87 [95% CI, 0.79-0.96]; P =.004). Bempedoic acid was also associated with significant reductions in risk for the composite of CV death, nonfatal stroke, or nonfatal MI (8.2 vs 9.5% for placebo; HR, 0.85 [95% CI, 0.76-0.96]; P =.006), fatal or nonfatal MI (3.7% vs 4.8% for placebo; HR, 0.77 [95% CI, 0.66-0.91]; P =.002), and coronary revascularization (6.2% vs 7.6% for placebo; HR, 0.81 [95% CI, 0.72-0.92]; P =.001).
As for safety, the incidences of gout (3.1%) and cholelithiasis (2.2%) were higher with bempedoic acid compared with placebo (2.1% and 1.2%, respectively). Small increases in serum creatinine, uric acid, and liver enzymes were also reported more frequently with bempedoic acid.
“These results are practice changing and exceed our expectations,” said Sheldon Koenig, president and CEO of Esperion. “We expect applicable treatment guidelines to be updated quickly which will then lead to a paradigm shift in patient care. Based upon the strength of the data and the clinical significance they represent, we will be filing with the FDA and EMA by June 2023 and anticipate receipt of expanded CV risk reduction labels in 1H 2024 that will more than double the addressable treatment population for Nexletol and Nexlizet.”
- Landmark CLEAR Outcomes study demonstrates Nexletol® (bempedoic acid) Tablet is the only LDL-C lowering therapy since statins to reduce hard ischemic events in a broad population of both primary prevention and secondary prevention patients. News release. Esperion. March 4, 2023. Accessed March 6, 2023. https://www.globenewswire.com/news-release/2023/03/04/2620613/0/en/Landmark-CLEAR-Outcomes-Study-Demonstrates-NEXLETOL-bempedoic-acid-Tablet-is-the-Only-LDL-C-Lowering-Therapy-Since-Statins-to-Reduce-Hard-Ischemic-Events-in-a-Broad-Population-of-B.html.
- Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. Esperion. Published online March 4, 2023. doi:10.1056/NEJMoa2215024