What is bempedoic acid?

Bempedoic acid is the novel active ingredient in NEXLETOL, as well as the main component of NEXLIZET (in addition to ezetimibe), that has been shown to significantly reduce LDL-C levels when added to other lipid-lowering therapies. Bempedoic acid was studied in clinical trials of patients with ASCVD or HeFH who needed additional LDL-C lowering on top of maximally tolerated statin therapy.1-5

How were the clinical trials for NEXLETOL designed, and what were the endpoints?

CLEAR Harmony 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. The primary endpoint was general safety, which included adverse events, clinical safety laboratories, physical examinations, vital signs, and electrocardiogram. A secondary endpoint was % change from baseline to Week 12 in LDL-C.3

CLEAR Wisdom 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. The 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.4

How was the clinical trial for NEXLIZET designed, and what were the endpoints?

053 Trial was a 12-week, randomized, double-blind, Phase 3 trial in 301 patients randomized 2:2:2:1 to receive NEXLIZET (n=86), NEXLETOL (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), either alone or with other lipid-lowering therapies. The primary endpoint was % change from baseline to Week 12 in LDL-C. A secondary endpoint was % change from baseline to Week 12 in hsCRP, non-HDL-C, total C, apolipoprotein B, HDL-C, and TGs.2,5

What background lipid-lowering therapies were included in the clinical trials for NEXLETOL?

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.1,3,4

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.1

What background lipid-lowering therapies were included in the clinical trial for NEXLIZET?

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; rosuvastatin 20 mg to 40 mg.2,5

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.2

Additionally, if coadministered with2:

  • 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
What was the impact of NEXLETOL on LDL-C?

In the primary analysis populations, CLEAR Harmony results showed a significant 18% mean LDL-C reduction with NEXLETOL compared to placebo (P<0.001), and CLEAR Wisdom showed a significant 17% mean LDL-C reduction with NEXLETOL compared to placebo (P<0.001), for extra control on top of a statin. LDL-C reductions were also achieved in the subgroup populations: patients taking low-, moderate-, and high-intensity statins.1,3,4

What was the impact of NEXLIZET on LDL-C?

053 Trial results showed a significant 38% mean LDL-C reduction with NEXLIZET compared to placebo (P<0.001), for extra control on top of a statin.2

What were the most common AEs reported in the clinical trials for NEXLETOL?

In the clinical trials for NEXLETOL, the most common AEs 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.1

What were the most common AEs reported in the clinical trial for NEXLIZET?

In the clinical trial for NEXLIZET, the most common AEs 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.5

To learn more about the incidence of AEs occurring in pivotal trials of NEXLETOL or ezetimibe that did not occur at a significant rate in the pivotal trial of NEXLIZET, click here.2

What are the mechanisms of action of NEXLETOL and NEXLIZET?

Bempedoic acid is the active ingredient in NEXLETOL, as well as the main component of NEXLIZET (in addition to ezetimibe). Bempedoic acid is the only ACL inhibitor, with an innovative mechanism of action complementary to statins. 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.1,2,6-8

NEXLETOL is a prodrug that is activated by ACSVL1, primarily in the liver. Since ACSVL1 is not present in skeletal muscle, NEXLETOL is not converted to its active moiety within skeletal muscle.1,7

NEXLIZET combines the active ingredient in NEXLETOL with ezetimibe, which combines the inhibition of ACL with reduction of cholesterol uptake in the small intestine.2,7,9

How are NEXLETOL and NEXLIZET administered and what are the dosing regimens?

NEXLETOL and NEXLIZET offer simple, 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. NEXLETOL is dosed as one 180-mg bempedoic acid tablet for all appropriate patients. NEXLIZET is dosed as one 180-mg bempedoic acid/10-mg ezetimibe combination tablet for all appropriate patients.1,2

NEXLETOL and NEXLIZET are appropriate for a range of patient types requiring added LDL-C lowering on top of a maximally tolerated statin therapy, including patients with ASCVD or HeFH.1-3,5,10-12

How can eligible patients save on their NEXLETOL or NEXLIZET prescriptions?

The NEXLETOL & NEXLIZET Co-Pay Card Program can help your eligible patients pay as little as $10 per fill for up to a 3-month supply of their prescription.* Your patients can assess their eligibility and enroll for a Co-Pay Card online at NexCopay.com. They can also call 1-855-699-8814 (8:00AM-8:00PM ET, Monday-Friday, excluding holidays) for questions or to enroll.

*Certain restrictions apply. See Terms and Conditions.

LDL-C=low-density lipoprotein cholesterol; ASCVD=atherosclerotic cardiovascular disease; HeFH=heterozygous familial hypercholesterolemia; CLEAR=Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen; non-HDL-C=non-high-density lipoprotein cholesterol; total C=total cholesterol; hsCRP=high-sensitivity C-reactive protein; TGs=triglycerides; AE=adverse event; ACL=adenosine triphosphate citrate lyase; ACSVL1=very long-chain acyl-coenzyme A synthetase-1.

References: 1. NEXLETOL. Prescribing information. ESPERION Therapeutics, Inc.; 2020. 2. NEXLIZET. Prescribing information. ESPERION Therapeutics, Inc.; 2020. 3. Data on file. CSR 1002-040. October 2018. 4. Data on file. CSR 1002-047. January 2019. 5. Data on file. CSR 1002-053. January 2019. 6. Saeed A, Ballantyne CM. Bempedoic acid (ETC-1002): a current review. Cardiol Clin. 2018;36(2):257-264. 7. Pinkosky SL, Newton RS, Day EA, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016;7(13457):1-13. 8. Pinkosky SL, Filippov S, Srivastava RA, et al. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J Lipid Res. 2013;54(1):134-151. 9. ZETIA. Prescribing information. Merck & Co., Inc.; 2013. 10. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350. 11. Gidding SS, Champagne MA, de Ferranti SD, et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation. 2015;132(22):2167-2192. 12. Diagnosis & Management. The FH Foundation. Accessed February 19, 2020. https://thefhfoundation.org/diagnosis-management