Effective Date

Date of Origin 

07-01-2024            

10-01-2020

Nexletol®

(bempedoic acid)

Tablet

Reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with:

• established cardiovascular disease (CVD), or
• a high risk for a CVD event but without established CVD

Adjunct to diet, in combination with other low-density lipoprotein cholesterol (LDL-C) lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)

1

Nexlizet®

(bempedoic acid/ezetimibe)

Tablet

Reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with:

• established cardiovascular disease (CVD), or
• a high risk for a CVD event but without established CVD

Adjunct to diet, alone or in combination with other LDL-C lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH

2

Familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a common yet underdiagnosed autosomal dominant disorder that affects 1 in 220 individuals globally. An individual who is heterozygous for FH (HeFH) has a 50% chance of passing the gene to his or her children. FH is characterized by lifelong elevation of low-density lipoprotein cholesterol (LDL-C) and, if untreated, leads to early-onset atherosclerosis and increased risk of cardiovascular events. Affected men and women who are untreated have a 30% to 50% risk of a fatal or nonfatal cardiac event by ages 50 and 60 years, respectively. FH is generally a silent disease. Given the broad range of causes of hypercholesterolemia and early-onset coronary artery disease (CAD), it is not surprising that FH is not always in the differential diagnosis for healthcare professionals when confronted with a patient presenting with early CAD. Although diagnosis can be made on the basis of clinical features, genetic testing may offer additional insight regarding cardiac risk and diagnosis. There are no internationally agreed-upon criteria for the diagnosis of FH, so useful diagnostic criteria have been developed. Two of the criteria, the UK Simon Broome system and the Dutch Lipid Clinic Network criteria incorporate genetic tests into their algorithm.(3)

Management

Since publication of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol, three additional non-statin therapies have received FDA approval for management of hypercholesterolemia (bempedoic acid, evinacumab, inclisiran). The American College of Cardiology (ACC) recognized that clinicians, patients, and payers may seek more specific recommendations on when to use newer non-statin therapies if the response to statin therapy, ezetimibe, and/or PCSK9 inhibitors is deemed inadequate. The 2022 ACC Consensus Decision Pathway was designed to address current gaps in care for LDL-C lowering to reduce ASCVD risk and provides further recommendations regarding the use of newer non-statin therapies.(8,9)

The key updates that the 2022 ACC Consensus Pathway recommend are for adults with ASCVD at very high risk on a maximally tolerated statin therapy that require additional lowering of LDL-C (patient has achieved<50% reduction in LDL-C or LDL-C greater than or equal to 55 mg/dL or non–HDL-C greater than or equal to 85 mg/dL) despite maximally tolerated statin therapy, a PCSK9 inhibitor and/or ezetimibe are preferred as the initial non-statin therapy followed by bempedoic acid or inclisiran for further LDL-C lowering. For adults with ASCVD NOT at very high risk on a maximally tolerated statin therapy that require additional lowering of LDL-C C (patient has achieved<50% reduction in LDL-C or LDL-C greater than or equal to 70 mg/dL or non–HDL-C greater than or equal to 100 mg/dL) despite maximally tolerated statin therapy, when considering the addition of a non-statin therapy, ezetimibe is the preferred initial non-statin followed by adding or replacing with a PCSK9 inhibitor, then trying bempedoic acid or inclisiran.(8)

The CLEAR Outcomes trial was a double-blind trial conducted in 32 countries and included 13,970 patients who were unable or unwilling to take guideline-recommended doses of statins that were randomized to oral bempedoic acid 180 mg daily or placebo and followed for a median of 3.4 years that was completed November 7th, 2022. The primary end point was a four-component composite of major adverse cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The results of this trial indicate among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization).(7)

Safety

Nexletol is contraindicated in patients with known hypersensitivity to any excipients in the product.(1)

Nexlizet is contraindicated in patients with known hypersensitivity to ezetimibe tablets or any excipients in the product.(2)

1

Nexletol prescribing information. Esperion Therapeutics, Inc. March 2024.

2

Nexlizet prescribing information. Esperion Therapeutics, Inc. March 2024.

3

McGowan MP, Dehkordi SHH, Moriarty PM, Duell PB. Diagnosis and treatment of heterozygous familial hypercholesterolemia. Journal of the American Heart Association. 2019;8(24). doi:10.1161/jaha.119.013225

4

Reference no longer used.

5

Reference no longer used.

6

Reference no longer used.

7

Nissen SE, Lincoff AM, Brennan DM, et al. Bempedoic acid and cardiovascular outcomes in Statin-Intolerant patients. The New England Journal of Medicine. 2023;388(15):1353-1364. doi:10.1056/nejmoa2215024

8

Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC Expert Consensus Decision Pathway on the role of nonstatin therapies for LDL-Cholesterol Lowering in the management of atherosclerotic cardiovascular Disease risk. Journal of the American College of Cardiology. 2022;80(14):1366-1418. doi:10.1016/j.jacc.2022.07.006

9

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. Circulation. 2019;139(25). doi:10.1161/cir.0000000000000625

10

Reference no longer used.

11

Reference no longer used.

Nexletol

bempedoic acid tab

180 MG

M ; N ; O ; Y

N

Nexlizet

bempedoic acid-ezetimibe tab

180-10 MG

M ; N ; O ; Y

N

Nexletol

bempedoic acid tab

180 MG

30

Tablets

30

DAYS

Nexlizet

bempedoic acid-ezetimibe tab

180-10 MG

30

Tablets

30

DAYS

Nexletol

bempedoic acid tab

180 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Nexlizet

bempedoic acid-ezetimibe tab

180-10 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Nexletol

bempedoic acid tab

180 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Nexlizet

bempedoic acid-ezetimibe tab

180-10 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PA

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. BOTH of the following:
      1. ONE of the following:
         1. The patient has a diagnosis of primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) OR
         2. The patient is using the requested agent to reduce the risk of myocardial infarction and coronary revascularization AND ONE of the following:
            1. The patient has established cardiovascular disease (CVD) OR
            2. The patient has a high risk for a CVD event AND
      2. ONE of the following:
         1. The patient has tried and had an inadequate response to at least ONE statin OR
         2. The patient has an intolerance or hypersensitivity to statin therapy OR
         3. The patient has an FDA labeled contraindication to ALL statins OR
   2. The patient has another FDA labeled indication for the requested agent and route of administration OR
   3. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following criteria are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS or DrugDex 1 or 2a level of evidence

Length of approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. 

QL with PA

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of approval: up to 12 months