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ph-1173

Bempedoic Acid Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1173

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
10/1/2022

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Nexletol™ (bempedoic acid) Tablet	Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Limitation of Use: The effect of bempedoic acid on cardiovascular morbidity and mortality has not been determined.		1
Nexlizet™ (bempedoic acid/ezetimibe) Tablet	Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Limitation of Use: The effect of bempedoic acid on cardiovascular morbidity and mortality has not been determined.		2

Agent(s)

FDA Indication(s)

Notes

Ref#

Nexletol™

(bempedoic acid)

Tablet

Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.

Limitation of Use:

The effect of bempedoic acid on cardiovascular morbidity and mortality has not been determined.

Nexlizet™

(bempedoic acid/ezetimibe)

Tablet

Limitation of Use:

The effect of bempedoic acid on cardiovascular morbidity and mortality has not been determined.

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

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.

Heterozygous familial hypercholesterolemia (HeFH)

The Simon Broome Register criteria and Dutch Lipid clinic Network criteria have been developed to aid in diagnosing HeFH.(5)Definitive diagnosis of HeFH according to Simon Broome diagnostic criteria requires the patient has one of the following:(4,5)

- Total cholesterol greater than 6.7 mmol/L or low-density lipoprotein cholesterol (LDL-C) greater than 4.0 mmol/L in a child aged younger than 16 years, or greater than 7.5 mmol/L or LDL-C greater than 4.9 mmol/L in an adult (levels either pre-treatment or highest on treatment) plus tendon xanthomas in the patient, or in first-degree relative (parent, sibling or child), or in second-degree relative (e.g., grandparent, uncle or aunt)
- DNA-based evidence of an LDL receptor mutation, familial defective Apo B-100, or a PCSK9 mutation

The Dutch Lipid Clinic Network criteria assign points based on cholesterol levels, family history of hyperlipidemia or cardiovascular disease, clinical presentation, and/or presence of identified genetic mutation affecting plasma LDL-C.(5-7) A definitive diagnosis of HeFH can be made in patients with greater than 8 points.

Dutch Lipid Clinic Network criteria for diagnosis of heterozygous familial hypercholesterolemia.(8)

Group 1: Family history	Points
First-degree relative with known premature (less than 55 years, men; ;less than 60 years, women) coronary heart disease (CHD) First-degree relative with known LDL cholesterol greater than 95th percentile by age and gender for country First-degree relative with tendon xanthoma and/or corneal arcus Children less than 18 years with LDL cholesterol greater than 95th percentile by age and gender for country	1 1 2 2
Group 2: Clinical history	Points
Subject has premature (less than 55 years, men; less than 60 years, women) CHD Subject has premature (less than 55 years, men; less than 60 years, women) cerebral or peripheral vascular disease	2 1
Group 3: Physical examination	Points
Tendon xanthoma Corneal arcus in a person less than 45 years	6 4
Group 4: Biochemical results (LDL-C)	Points
Greater than .5 mmol/L (greater than 325 mg/dL) 6.5–8.4 mmol/L (251–325 mg/dL) 5.0–6.4 mmol/L (191–250 mg/dL) 4.0–4.9 mmol/L (155–190 mg/dL)	8 5 3 1
Group 5: Molecular genetic testing (DNA analysis)	Points
Causative mutation shown in the LDLR, APOB, or PCSK9 genes	8
Use and Interpretation
Assign only one score, the highest applicable, per group then add the points from each group to achieve the total score Definitive FH diagnosis: Greater than 8 points Probable FH diagnosis: 6 to 8 points Possible FH diagnosis: 3 to 5 points Unlikely FH diagnosis: 0 to 2 points

Atherosclerotic Cardiovascular Disease (ASCVD) Secondary Prevention

The AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline lists the following as clinical ASCVD:(9)

Acute coronary syndrome (ACS)
Myocardial infarction (MI)
Stable or unstable angina or coronary or other arterial revascularization
Stroke
Transient ischemic attack (TIA) or peripheral artery disease (PAD) including aortic aneurysm

Safety

Nexletol has no contraindication or black box warnings.(1)

Nexlizet has no black box warnings, but has the following contraindication:(2)

Known hypersensitivity to ezetimibe tablets

REFERENCES

Number	Reference
1	Nexletol prescribing information. Esperion Therapeutics, Inc. September 2021.
2	Nexlizet prescribing information. Esperion Therapeutics, Inc. September 2021.
3	McGowan MP, Dehkordi SH, Moriarty PM, et. Al. “Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia”. JAHA 8 (24) 2019. Available at: https://www.ahajournals.org/doi/10.1161/JAHA.119.013225
4	Identification and Management of Familial Hypercholesterolemia. Simon Broome Diagnostic criteria for index individuals and relatives. Available at: http://www.ncbi.nlm.nih.gov/books/NBK53810/
5	National Collaborating Centre for Primary Care (UK). Identification and Management of Familial Hypercholesterolaemia (FH) [Internet]. London: Royal College of General Practitioners (UK); 2008 Aug. (NICE Clinical Guidelines, No. 71.) 3, Diagnosis. Available from: https://www.nice.org.uk/guidance/CG71
6	World Health Organization. Familial Hypercholesterolaemia (FH): Report of a second WHO consultation. Geneva: World Health Organization; 1999 Available at: https://apps.who.int/iris/handle/10665/66346
7	Nordestgaard BG, Chapman MJ, Humphries ST, et al; for the European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J. 2013. doi.10.1093/eurheartj/eht273. https://pubmed.ncbi.nlm.nih.gov/23956253/
8	Gidding S, Champagne M, Ferranti S, et al. The Agenda for Familial Hypercholesterolemia. A Scientific Statement From the American Heart Association. Circulation. 2015; 132:00-00 https://www.ahajournals.org/doi/10.1161/CIR.0000000000000297
9	2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Journal of the American College of Cardiology. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Agent Names	Strength	Targeted MSC	Available MSC	Effective Date

NEXLETOL*bempedoic acid tab	180 MG	M ; N ; O ; Y	N
NEXLIZET*bempedoic acid-ezetimibe tab	180 MG	M ; N ; O ; Y	N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Agent GPI	Agent Names	Strength	QL Amount	Dose Form	Days Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist	Effective Date

393800200003	NEXLETOL*bempedoic acid tab	180 MG	30.0	TABS	30	Days
399910022003	NEXLIZET*bempedoic acid-ezetimibe tab	180 MG	30.0	TABS	30	Days

CLIENT SUMMARY – PRIOR AUTHORIZATION

Agent Names	Strength	Client Formulary
NEXLETOL*bempedoic acid tab	180 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
NEXLIZET*bempedoic acid-ezetimibe tab	180 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Agent Names	Strength	Client Formulary
NEXLETOL*bempedoic acid tab	180 MG
NEXLIZET*bempedoic acid-ezetimibe tab	180 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Initial Evaluation Target Agent(s) will be approved when ALL of the following are met: ONE of the following: BOTH of the following: The patient has ONE of the following: A diagnosis of heterozygous familial hypercholesterolemia (HeFH) confirmed by ONE of the following: Genetic confirmation of one mutant allele at the LDLR, Apo-B, PCSK9, or ARH adaptor protein 1/LDLRAP1 gene locus OR BOTH of the following: ONE of the following: History of total cholesterol greater than 290 mg/dL (greater than 7.5 mmol/L) (pretreatment or highest level while on treatment) OR History of LDL-C greater than 190 mg/dL (greater than 4.9 mmol/L) (pretreatment or highest level while on treatment) AND History of tendon xanthomas in ONE of the following: The patient OR The patient’s first degree relative (i.e., parent, sibling, or child) OR The patient’s second degree relative (e.g., grandparent, uncle, or aunt) OR The Patient has a Dutch Lipid Clinic Network Criteria score of greater than 5 OR A diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) defined as having ONE of the following: Acute coronary syndrome History of myocardial infarction Stable or unstable angina Coronary or other arterial revascularization Stroke Transient ischemic attack Peripheral arterial disease, including aortic aneurysm, presumed to be of atherosclerotic origin AND ONE of the following: The patient is on maximally tolerated statin therapy OR The patient has an intolerance or hypersensitivity to statin therapy OR The patient has an FDA labeled contraindication to ALL statins OR The patient has another FDA approved indication for the requested agent and route of administration OR The patient has another indication that is supported in compendia for the requested agent and route of administration AND ONE of the following: The patient’s age is within FDA labeling for the requested indication for the requested agent OR The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication AND 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. Renewal Evaluation Target Agent(s) will be approved for renewal when ALL of the following criteria are met: The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND The patient has had clinical benefit with the requested agent AND If the patient has ASCVD or HeFH, then ONE of the following: The patient is on maximally tolerated statin therapy OR The patient has an intolerance or hypersensitivity to statin therapy OR The patient has an FDA labeled contraindication to ALL statins AND 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.

Module

Clinical Criteria for Approval

Initial Evaluation

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

ONE of the following:
1. BOTH of the following:
  1. The patient has ONE of the following:
    1. A diagnosis of heterozygous familial hypercholesterolemia (HeFH) confirmed by ONE of the following:
      1. Genetic confirmation of one mutant allele at the LDLR, Apo-B, PCSK9, or ARH adaptor protein 1/LDLRAP1 gene locus OR
      2. BOTH of the following:
        
        ONE of the following:
        
        History of total cholesterol greater than 290 mg/dL (greater than 7.5 mmol/L) (pretreatment or highest level while on treatment) OR
        
        History of LDL-C greater than 190 mg/dL (greater than 4.9 mmol/L) (pretreatment or highest level while on treatment) AND
        
        History of tendon xanthomas in ONE of the following:
        
        The patient OR
        
        The patient’s first degree relative (i.e., parent, sibling, or child) OR
        
        The patient’s second degree relative (e.g., grandparent, uncle, or aunt) OR
      3. The Patient has a Dutch Lipid Clinic Network Criteria score of greater than 5 OR
    2. A diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) defined as having ONE of the following:
      1. Acute coronary syndrome
      2. History of myocardial infarction
      3. Stable or unstable angina
      4. Coronary or other arterial revascularization
      5. Stroke
      6. Transient ischemic attack
      7. Peripheral arterial disease, including aortic aneurysm, presumed to be of atherosclerotic origin AND
  2. ONE of the following:
    1. The patient is on maximally tolerated statin therapy 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 approved 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
ONE of the following:
1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
2. The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication AND
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.

Renewal Evaluation

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

The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND
The patient has had clinical benefit with the requested agent AND
If the patient has ASCVD or HeFH, then ONE of the following:
1. The patient is on maximally tolerated statin therapy OR
2. The patient has an intolerance or hypersensitivity to statin therapy OR
3. The patient has an FDA labeled contraindication to ALL statins AND
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.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: ONE of the following: The requested quantity (dose) does NOT exceed the program quantity limit OR ALL of the following: The requested quantity (dose) is greater than the program quantity limit AND The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR ALL of the following: The requested quantity (dose) is greater than the program quantity limit AND The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication AND The prescriber has provided information in support of therapy with a higher dose for the requested indication Length of Approval: 12 months

Module

Clinical Criteria for Approval

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

ONE of the following:
1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
  1. The requested quantity (dose) is greater than the program quantity limit AND
  2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
  3. 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. ALL of the following:
  1. The requested quantity (dose) is greater than the program quantity limit AND
  2. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication AND
  3. The prescriber has provided information in support of therapy with a higher dose for the requested indication

Length of Approval: 12 months

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

BCBSAL _ PS _ Bempedoic Acid Prior Authorization with Quantity Limit _ProgSum_ 10/1/2022 _