Frequently Asked Questions

Bempedoic acid is the active ingredient in NEXLETOL, as well as a component of NEXLIZET (in addition to ezetimibe), that has been shown to significantly reduce LDL-C levels when added to diet and maximally tolerated statins. Bempedoic acid was studied in clinical trials of patients with ASCVD and/or HeFH who needed additional LDL-C lowering on top of diet and maximally tolerated statin therapy.^1-3

053 Trial (Study 1) was a 12-week, randomized, double-blind, Phase 3 trial in 301 patients randomized 2:2:2:1 to receive NEXLIZET (n=86), bempedoic acid (n=88), ezetimibe (n=86), or placebo (n=41). 053 Trial included patients aged ≥18 years with fasting LDL-C ≥100 mg/dL if they had ASCVD and/or HeFH, or ≥130 mg/dL if they had multiple cardiovascular risk factors. Therapies were added to whatever patient’s maximally tolerated statin dose was (including no statin at all). Primary endpoint was % change from baseline to Week 12 in LDL-C. Secondary endpoint was % change from baseline to Week 12 in hsCRP, non-HDL-C, total C, apolipoprotein B, HDL-C, and TGs.^1,2

CLEAR Harmony (Study 1) was a 52-week, randomized, double-blind, Phase 3 trial in 2,230 patients randomized 2:1 to receive NEXLETOL (n=1,488) or placebo (n=742). CLEAR Harmony included patients aged ≥18 years with fasting LDL-C ≥70 mg/dL, and high-risk patients with ASCVD and/or HeFH. NEXLETOL was added to whatever patient’s maximally tolerated statin dose was, either alone or with other lipid-lowering therapies. Primary endpoint was general safety, which included ARs, clinical safety laboratories, physical examinations, vital signs, and electrocardiogram. Secondary endpoint was % change from baseline to Week 12 in LDL-C⁠.⁠^4,5

CLEAR Wisdom (Study 2) was a 52-week, randomized, double-blind, Phase 3 trial in 779 patients randomized 2:1 to receive NEXLETOL (n=522) or placebo (n=257). CLEAR Wisdom included patients aged ≥18 years with fasting LDL-C ≥70 mg/dL, and high-risk patients with ASCVD and/or HeFH. NEXLETOL was added to whatever patient’s maximally tolerated statin dose was (including no statin at all), either alone or with other lipid-lowering therapies. Primary endpoint was % change from baseline to Week 12 in LDL-C. Secondary endpoints were % change from baseline to Week 24 in LDL-C, % change from baseline to Week 12 in non-HDL-C, total C, apolipoprotein B, and hsCRP, and absolute change from baseline to Weeks 12 and 24 in LDL-C.^6,7

In addition to NEXLIZET, patients receiving maximally tolerated statin therapy were included in the clinical trial. High-intensity statins included: atorvastatin 40 mg to 80 mg and rosuvastatin 20 mg to 40 mg.^1,2

When NEXLIZET is coadministered with simvastatin, limit simvastatin dosage to 20-mg daily. When NEXLIZET is coadministered with pravastatin, limit pravastatin dosage to 40-mg daily.¹

When NEXLIZET is coadministered with¹:

• Simvastatin or Pravastatin: Coadministration with bempedoic acid results in increased concentrations and increased risk of simvastatin- or pravastatin-related myopathy. Use of NEXLIZET with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided
• Cyclosporine: Monitor cyclosporine concentrations; the potential effects of the increased exposure to ezetimibe from concomitant use should be carefully weighed against the benefits of alterations in lipid levels provided by NEXLIZET
• Fibrates: Coadministration of NEXLIZET with fibrates other than fenofibrate is not recommended. Fenofibrate and ezetimibe may increase cholesterol excretion into the bile, leading to cholelithiasis
• Cholestyramine: Concomitant use with NEXLIZET decreases ezetimibe concentration. This may result in a reduction of efficacy. Administer NEXLIZET either at least 2 hours before, or at least 4 hours after, bile acid sequestrants

In addition to NEXLETOL, patients receiving maximally tolerated statin therapy were included in the clinical trials. Low-intensity statins included: simvastatin 10 mg; pravastatin 10 mg to 20 mg; lovastatin 20 mg; fluvastatin 20 mg to 40 mg; pitavastatin 1 mg; low-intensity statins also included those patients taking low-dose statins using an alternate regimen (ie, every other day, or for a specified number of times per week) and those unable to tolerate any statin at any dose. Moderate-intensity statins included: atorvastatin 10 mg to 20 mg; rosuvastatin 5 mg to 10 mg; simvastatin 20 mg to 40 mg; pravastatin 40 mg to 80 mg; lovastatin 40 mg; fluvastatin XL 80 mg; fluvastatin 40 mg; pitavastatin 2 mg to 4 mg. High-intensity statins included: atorvastatin 40 mg to 80 mg; rosuvastatin 20 mg to 40 mg.^4,6

When NEXLETOL is coadministered with simvastatin, limit simvastatin dosage to 20-mg daily. When NEXLETOL is coadministered with pravastatin, limit pravastatin dosage to 40-mg daily.³

053 Trial results showed a significant 38% mean LDL-C reduction with NEXLIZET compared to placebo at 12 weeks (P<0.001), for extra control on top of a statin.¹

In the primary analysis populations, CLEAR Harmony results showed a significant 18% mean LDL-C reduction with NEXLETOL compared to placebo at 12 weeks (P<0.001), and CLEAR Wisdom results showed a significant 17% mean LDL-C reduction with NEXLETOL compared to placebo at 12 weeks (P<0.001), for extra control on top of a statin. LDL-C reductions were also achieved in the subgroup populations: patients taking low to moderate and high-intensity statins.^3-7

In the clinical trial for NEXLIZET, the most common ARs reported in ≥3% of patients in the NEXLIZET group were: urinary tract infection, nasopharyngitis, constipation, back pain, fatigue, upper respiratory tract infection, blood creatinine increased, blood uric acid increased, and bronchitis.^1,8

To learn more about the incidence of ARs occurring in pivotal trials of bempedoic acid or ezetimibe that did not occur at a significant rate in the pivotal trial of NEXLIZET, please visit our NEXLIZET safety page.¹

In the clinical trials for NEXLETOL, the most common ARs reported in ≥2% of patients with ASCVD and HeFH using NEXLETOL (and more frequently than with placebo) were: upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes.³

NEXLIZET and NEXLETOL offer oral, once-daily dosing with the flexibility to be combined with existing lipid-lowering medications for appropriate patients.* They can be taken with or without food and no titration is necessary. NEXLIZET is dosed as one 180-mg bempedoic acid/10-mg ezetimibe tablet for all appropriate patients.^† NEXLETOL is dosed as one 180-mg bempedoic acid tablet for all appropriate patients.^1,3

NEXLIZET and NEXLETOL are appropriate for a range of patient types requiring added LDL-C lowering on top of diet and a maximally tolerated statin therapy, including a range of ASCVD patient types as well as HeFH patients.^1-3

Bempedoic acid is the active ingredient in NEXLETOL, as well as a component of NEXLIZET (in addition to ezetimibe).^1,3,9-11

Bempedoic acid is the first and only ACL inhibitor, working complementary to statins to lower LDL-C. It works along the cholesterol biosynthesis pathway, 2 steps upstream from the primary target of statins. By inhibiting ACL, bempedoic acid decreases cholesterol biosynthesis, resulting in upregulation of LDL receptors and increased clearance of LDL-C from the bloodstream.^1,3,9-11

NEXLIZET also contains ezetimibe, which reduces cholesterol absorption in the intestine. Ezetimibe decreases hepatic cholesterol stores, lowering circulating LDL-C⁠.⁠^1,3,9-11