Pharmacy Policy Bulletin
PCSK9 Inhibitors – Commercial and Healthcare Reform
Number: J-0434 Category: Prior Authorization
Line(s) of Business:

Commercial
Healthcare Reform
Medicare

Benefit(s):

Commercial:

Prior Authorization (1.):

1.  PCSK-9 = Yes w/ Prior Authorization

 

Healthcare Reform: Not Applicable
Region(s):

All
Delaware
New York
Pennsylvania
West Virginia

Additional Restriction(s):

None


Drugs Products
  • Praluent (alirocumab)
  • Repatha (evolocumab)
  • Repatha (evolocumab) SureClick
  • Repatha (evolocumab) Pushtronex
FDA-Approved Indications:
  • Praluent
    • To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.
    • As adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol LDL-C.
  • Repatha
    • To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
    • As an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe) for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C).
    • As an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional LDL-C lowering.


Background:
  • The PCSK9 enzyme binds to LDL receptors present on the surface of hepatocytes and degrades the receptors. This results in fewer LDL receptors available on hepatocytes to remove excess LDL-C from the blood. Therefore, PCSK9 inhibitors hinder this process and lower LDL levels.
  • Clinical atherosclerotic cardiovascular disease (ASCVD) includes acute coronary syndromes, or a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin. Repatha (evolocumab) and Praluent (alirocumab) are indicated in patients with established ASCVD and hyperlipidemia and thus should only be used as secondary prophylaxis to prevent an additional cardiovascular event.
  • Guideline based treatment options that should be considered for the management of blood cholesterol including the following:
    • All individuals encouraged to live a heart-healthy lifestyle throughout their life.
    • In patients with clinical ASCVD, reduce LDL-C with high-intensity statin therapy or maximally tolerated statin therapy. Use a maximally tolerated statin to lower LDL-C levels by ≥ 50%.
    • If very high-risk ASCVD, use a LDL-C threshold of 70 mg/dL and consider addition of non-statins to statin therapy. It is reasonable to add ezetimibe to maximally tolerated statin therapy when the LDL-C level remains ≥ 70 mg/dL. If LDL-C remains ≥ 70 mg/dL while on maximally tolerated statin and ezetimibe, add PCSK9 inhibitor.
    • In patients with severe primary hypercholesterolemia (LDL-C level ≥ 190 mg/dL), without calculating 10-year ASCVD risk, begin high-intensity statin therapy. If LDL-C levels remain ≥ 100 mg/dL, add ezetimibe. If LDL-C continues to be above goal while on statin plus ezetimibe and has risk of ASCVD events, a PCSK9 inhibitor can be considered.
    • In patients 40 to 75 years of age with diabetes mellitus and LDL-C ≥ 70 mg/dL, start moderate-intensity statin therapy without calculating 10-year ASCVD risk.
    • In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥ 70 mg/dL at a 10-year ASCVD risk of ≥ 7.5%, start a moderate-intensity statin if a discussion of treatment options favors statin therapy.
    • In patients 30 to 75 years of age with HeFH of ≥ 100 mg/dL while taking maximally tolerated statin and ezetimibe therapy, the addition of a PCSK9 inhibitor may be considered.
    • HoFH treatment is recommended to be managed by a lipid specialist as care is beyond the scope of the guideline as it is harder to treat and more rare than HeFH.
  • The Simon Broom Criteria and Dutch Lipid Clinic Criteria are accepted resources for FH diagnosis. Dutch Lipid Clinic Network assigns points based on low density lipoprotein cholesterol levels, personal history of early ASCVD, family history of early ASCVD, or high cholesterol in a first-degree relative, and personal and physical examination findings. A score > 8 indicates a definitive familial hypercholesterolemia diagnosis. Simon Broom Criteria is based on the lipid profile in familial hypercholesterolemia, a family history of hypercholesterolemia and/or premature ischemic heart disease, or the presence of tendon xanthomata.
  • Prescribing Considerations:
    • In clinical trials, PCSK9 inhibitors were used in conjunction with statins. ACC/AHA guidelines continue to promote the use of statins for secondary prevention of cardiovascular events. As such, the importance of continued statin therapy should not be minimized.
    • The safety and effectiveness of Juxtapid in combination with a PCSK9 inhibitor has not been established for HoFH.
    • Maximally tolerated statin therapy is defined as the highest tolerated intensity and frequency of a statin, even if the dose is zero. If statin tolerance is zero the member meets the statin intolerance definition in the criteria.

 

Low-Intensity Statin Therapy

Moderate-Intensity Statin Therapy

High-Intensity Statin Therapy

Daily dose lowers LDL-C by < 30% on average

Daily dose lowers LDL-C by 30% to <50%, on average

Daily dose lowers LDL-C by ≥ 50%, on average
  • simvastatin 10 mg
  • pravastatin 10-20 mg
  • lovastatin 20 mg
  • fluvastatin 20-40 mg
  • pitavastatin 1 mg

 

 

 

 

 

  
  • atorvastatin 10-20 mg
  • rosuvastatin 5-10 mg
  • simvastatin 20-40 mg
  • pravastatin 40-80 mg
  • lovastatin 40 mg
  • fluvastatin XL 80 mg
  • fluvastatin 40 mg twice daily
  • pitavastatin 2-4 mg

 

 

 

 

 

  • atorvastatin 40-80 mg
  • rosuvastatin 20-40 mg

 

 

 

 

 

 

 

 


Approval Criteria

I.      Homozygous Familial Hypercholesterolemia (HoFH) (Repatha only)

 

A.    Initiation (< 6 months of therapy)

When a benefit, coverage of Repatha may be approved when all of the following criteria are met (1. through 4.):

1.     The member is 13 years of age or older.

2.     Repatha is being prescribed by or in consultation with one (1) of the following specialties (a., b., or c.):

a.     Cardiologist

b.    Lipid Specialist

c.     Endocrinologist

3.     The member has a diagnosis of HoFH supported by one (1) of the following criteria (a. or b.):

a.     Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus.

b.    The member meets all of the following criteria (i. and ii.):

i.      Untreated LDL-C level of > 500 mg/dL

ii.    The member meets one (1) of the follow criteria (A) or B)):

A)    Cutaneous or tendon xanthoma before 10 years of age

B)    Evidence of HeFH in both parents

4.     The member meets one (1) of the following criteria (a. or b.):

a.     The member has a LDL-C > 100 mg/dL despite use with a maximally tolerated statin.

b.    The member has a LDL-C > 100 mg/dL and the member is statin intolerant defined as one (1) of the following (i. or ii.):

i.      The member experienced statin related rhabdomyolysis or skeletal-related muscle symptoms while receiving at least two (2) separate trials of different statins which resolved upon discontinuation of the statins

ii.    The member experienced one (1) of the following during any course of statin therapy (A), B), or C)):

A)    Creatinine kinase (CK) increase to 10 times upper limit of normal (ULN)

B)    Liver function tests (LFTs) increase to 3 times ULN

C)    Hospitalization due to severe statin-related adverse event, such as rhabdomyolysis

 

B.    Maintenance (≥ 6 months of therapy)

When a benefit, reauthorization of Repatha may be approved when all of the following criteria are met (1. through 6.):

1.     The member is 13 years of age or older.

2.     Repatha is being prescribed by or in consultation with one (1) of the following specialties (a., b., or c.):

a.     Cardiologist

b.    Lipid Specialist

c.     Endocrinologist

3.     Prior to the start of therapy, the member has a diagnosis of HoFH supported by one (1) of the following criteria (a. or b.):

a.     Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus.

b.    The member meets all of the following criteria (i. and ii.):

i.      Untreated LDL-C level of > 500 mg/dL

ii.    The member meets one (1) of the follow criteria (A) or B)):

A)    Cutaneous or tendon xanthoma before 10 years of age

B)    Evidence of HeFH in both parents

4.     Prior to the start of therapy, the member had a LDL-C > 100 mg/dL despite use with a maximally tolerated statin.

5.     The member has experienced a reduction in LDL-C from baseline.

6.     The member has been adherent to Repatha therapy as evidenced by pharmacy claims.

 

II.    Heterozygous Familial Hypercholesterolemia (HeFH)

 

A.    Initiation (< 6 months of therapy)

When a benefit, coverage of Praluent or Repatha may be approved when all of the following criteria are met (1. through 5.):

1.     The member is 18 years of age or older.

2.     Repatha or Praluent is being prescribed by or in consultation with one of the following specialties (a., b., or c.):

a.     Cardiologist

b.    Lipid Specialist

c.     Endocrinologist

3.     The member has a diagnosis of HeFH supported by one (1) of the following (a., b., or c.):

a.     Genetic confirmation of one (1) mutant allele at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus.

b.    The member meets all of the following criteria (i. and ii):

i.      The member meets one (1) of the following criteria (A) or B)):

A)    Untreated LDL-C ≥ 190 mg/dL

B)    Untreated LDL-C ≥ 160 mg/dL before 20 years of age

ii.    The member meets one (1) of the following physical signs of familial hypercholesterolemia (A) through D)):

A)    tendon xanthoma

B)    corneal arcus prior to 45 years of age

C)    tuberous xanthoma

D)    xanthelasma

c.     The member meets one (1) of the following criteria (i. or ii.):

i.      WHO criteria/Dutch Lipid Clinical Network score > 8 points

ii.    Familial hypercholesterolemia possibility of “definite” based on the Simon Broome register

4.     The member meets one (1) of the following criteria (a. or b.):

a.     The member has a LDL-C > 100 mg/dL despite use with a maximally tolerated statin.

b.    The member has a LDL-C > 100 mg/dL and the member is statin intolerant defined as one (1) of the following (i. or ii.):

i.      The member experienced statin related rhabdomyolysis or skeletal-related muscle symptoms while receiving at least two (2) separate trials of different statins which resolved upon discontinuation of the statins

ii.    The member experienced one (1) of the following during any course of statin therapy (A), B), or C)):

A)    Creatinine kinase (CK) increase to 10 times ULN

B)    Liver function tests (LFTs) increase to 3 times ULN

C)    Hospitalization due to severe statin-related adverse event, such as rhabdomyolysis

5.     If the request is for Praluent, the member has experienced therapeutic failure or intolerance to Repatha. 

 

B.    Maintenance (≥ 6 months of therapy)

When a benefit, reauthorization of Praluent or Repatha may be approved when all of the following criteria are met (1. through 6.):

1.     The member is 18 years of age or older.

2.     Repatha or Praluent is being prescribed by or in consultation with one (1) of the following specialties (a., b., or c.):

a.     Cardiologist

b.    Lipid Specialist

c.     Endocrinologist

3.     Prior to the start of therapy, the member has a diagnosis of HeFH supported by one (1) of the following (a., b., or c.):

a.     Genetic confirmation of one (1) mutant allele at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus.

b.    The member meets all of the following criteria (i. and ii):

i.      The member meets one (1) of the following criteria (A) or B)):

A)    Untreated LDL-C ≥ 190 mg/dL

B)    Untreated LDL-C ≥ 160 mg/dL before 20 years of age

ii.    The member meets one (1) of the following physical signs of familial hypercholesterolemia (A) through D)):

A)    tendon xanthoma

B)    corneal arcus prior to 45 years of age

C)    tuberous xanthoma

D)    xanthelasma

c.     The member meets one (1) of the following criteria (i. or ii.):

i.      WHO criteria/Dutch Lipid Clinical Network score > 8 points

ii.    Familial hypercholesterolemia possibility of “definite” based on the Simon Broome register

4.     Prior to the start of therapy, the member had a LDL-C > 100 mg/dL despite use with a maximally tolerated statin.

5.     The member has experienced a reduction in LDL-C from baseline.

6.     The member has been adherent to Praluent or Repatha therapy as evidenced by pharmacy claims.

 

III.   Hypercholesterolemia with ASCVD

           

A.    Initiation (< 6 months of therapy)

When a benefit, coverage of Praluent or Repatha may be approved when all of the following criteria are met (1. through 4.):

1.     The member is 18 years of age or older.

2.     There is clinical documentation supporting the clinical ASCVD diagnosis including one (1) of the following (a. through g.):

a.     Acute coronary syndrome

b.    History of myocardial infarction

c.     Stable or unstable angina

d.    Coronary or other arterial revascularization

e.     History of stroke

f.      History of transient ischemic attack

g.    Peripheral arterial disease presumed to be of atherosclerotic origin

3.     The member meets one (1) of the following criteria (a. or b.):

a.     The member has a LDL-C > 70 mg/dL despite use with a maximally tolerated statin.

b.    The member has a LDL-C > 70 mg/dL and the member is statin intolerant defined as one (1) of the following (i. or ii.):

i.      The member experienced statin related rhabdomyolysis or skeletal-related muscle symptoms while receiving at least two (2) separate trials of different statins which resolved upon discontinuation of the statins

ii.    The member experienced one (1) of the following during any course of statin therapy (A), B), or C)):

A)    Creatinine kinase (CK) increase to 10 times upper limit of normal (ULN)

B)    Liver function tests (LFTs) increase to 3 times upper limit of normal (ULN)

C)    Hospitalization due to severe statin-related adverse event, such as rhabdomyolysis

4.     If the request is for Praluent, the member has experienced therapeutic failure or intolerance to Repatha.

 

B.    Maintenance (≥ 6 months of therapy)

When a benefit, reauthorization of Praluent or Repatha may be approved when all of the following criteria are met (1. through 5.):

1.     The member is 18 years of age or older.

2.     There is clinical documentation supporting the clinical ASCVD diagnosis including one (1) of the following (a. through g.):

a.     Acute coronary syndrome

b.    History of myocardial infarction

c.     Stable or unstable angina

d.    Coronary or other arterial revascularization

e.     History of stroke

f.      History of transient ischemic attack

g.    Peripheral arterial disease presumed to be of atherosclerotic origin

3.     Prior to the start of therapy, the member had a LDL-C > 70 mg/dL despite use with a maximally tolerated statin.

4.     The member meets one (1) of the following criteria (a. or b.):

a.     The member has experienced at least a 40% reduction in LDL-C from baseline.

b.    The member has a documented LDL-C < 70 mg/dL.

5.     The member has been adherent to Praluent or Repatha therapy as evidenced by pharmacy claims.

 

IV.   Primary Hyperlipidemia, Not Associated with ASCVD, HeFH, or HoFH

A.    Initiation (< 6 months of therapy)

When a benefit, initial authorization of Praluent and Repatha may be approved when all of the following criteria are met (1. through 5.):

1.     The member is 18 years of age or older.

2.     The member has a diagnosis of primary hyperlipidemia not associated with ASCVD, HeFH or HoFH.

3.     The member has a coronary artery calcium or calcification (CAC) score ≥ 300 Agatston units.

4.     The member meets one (1) of the following criteria (a. or b.):

a.     The member has a LDL-C > 70 mg/dL despite use with a maximally tolerated statin.

b.    The member has a LDL-C > 70 mg/dL and the member is statin intolerant defined as one (1) of the following (i. or ii.):

i.      The member experienced statin related rhabdomyolysis or skeletal-related muscle symptoms while receiving at least two (2) separate trials of different statins which resolved upon discontinuation of the statins

ii.    The member experienced one (1) of the following during any course of statin therapy (A), B), or C)):

A)    Creatinine kinase (CK) increase to 10 times ULN

B)    Liver function tests (LFTs) increase to 3 times ULN

C)    Hospitalization due to severe statin-related adverse event, such as rhabdomyolysis

5.     If the request is for Praluent, the member has experienced therapeutic failure or intolerance to Repatha.

 

B.    Maintenance (≥ 6 months of therapy)

When a benefit, reauthorization of Praluent or Repatha may be approved when all of the following criteria are met (1. through 6.):

1.     The member is 18 years of age or older.

2.     The member has a diagnosis of primary hyperlipidemia not associated with ASCVD, HeFH or HoFH.

3.     The member has a coronary artery calcium or calcification (CAC) score ≥ 300 Agatston units.

4.     Prior to the start of therapy, the member had a LDL-C > 70 mg/dL despite use with a maximally tolerated statin.

5.     The member meets one (1) of the following criteria (a. or b.):

a.     The member has experienced at least a 40% reduction in LDL-C from baseline.

b.    The member has a LDL-C < 70 mg/dL.

6.     The member has been adherent to Praluent or Repatha therapy as evidenced by pharmacy claims.

 

V.    An exception to some or all of the criteria above may be granted for select members and/or circumstances based on state and/or federal regulations.


Limitations of Coverage

I.      For HoFH, Repatha should be used in combination with other LDL-lowering therapies (e.g. statins, ezetimibe, LDL apheresis).

II.    The member is not using Repatha or Praluent in combination with Juxtapid or another PCSK9 inhibitor.

III.   Coverage of Praluent or Repatha for disease states outside of their FDA-approved indications should be denied based on the lack of clinical data to support their effectiveness and safety in other conditions.

IV.   For Commercial or HCR members with a closed formulary, a non-formulary product will only be approved if the member meets the criteria for a formulary exception in addition to the criteria outlined within this policy.


Authorization Duration

Initial Authorization

 

  • Commercial and HCR Plans: If approved, up to a 6 month authorization may be granted.

 

Reauthorization

 

  • Commercial and HCR Plans: If approved, up to a 12 month authorization may be granted.


Automatic Approval Criteria

None


Version: J-0434-014
Effective Date Begin: 03/04/2021
Effective End Begin: 06/08/2021
Original Date: 07/09/2015
Review Date: 12/02/2020


References:

  1. Praluent [package insert]. Bridgewater, NJ: Sanofi-Aventis and Regeneron Pharmaceuticals, Inc.; April 2019.
  2. Repatha [package insert]. Thousand Oaks, CA: Amgen Inc.; February 2019.
  3. Grundy SM, Stone NJ, Bailey AL, Beam C, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285-350.
  4. Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014 Aug 21; 35(32): 2146–2157.
  5. McGowan MP, Hosseini SH, Moriarty PM, Duell PB. Diagnosis and treatment of heterozygous familial hypercholesterolemia. JAHA. 2019; 8.
  6. Raal FJ, Hovingh GK, Catapano AL. Familial hypercholesterolemia treatments: guidelines and new therapies. Atherosclerosis. 2018. 277: 483-492.
  7. Ito MK and Watts GF. Challenges in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia. Drugs. 2015; 75(15): 1715–1724.

 

 




Pharmacy policies do not constitute medical advice, nor are they intended to govern physicians' prescribing or the practice of medicine. They are intended to reflect Highmark's coverage and reimbursement guidelines. Coverage may vary for individual members, based on the terms of the benefit contract.

Highmark retains the right to review and update its pharmacy policy at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the pharmacy policies is prohibited; however, limited copying of pharmacy policies is permitted for individual use.