Pharmacy Policy Bulletin

Policy Applies to

Commercial plans

Drugs Addressed in this Policy

Alirocumab (Praluent)
Evolocumab (Repatha/Repatha Pushtronex)

FDA-Approved Indications

· Alirocumab (Praluent): Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-cholesterol (LDL-C)

· Evolocumab (Repatha): Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-cholesterol (LDL-C)

Background

· 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.

· The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults makes the following statements:

o Lower-intensity statin therapy has been shown to reduce ASCVD events. Therefore, individuals that merit guideline-recommended statin therapy should be treated with the maximum appropriate intensity of a statin that does not cause adverse effects.

o The long-term adverse effects of statin-associated cases of diabetes over a 10-year period are unclear and are unlikely to be equivalent to a myocardial infarction, stroke, or ASCVD death.

o No evidence was found that titration or combination drug therapy to achieve specific LDL-C or non-HDL-C levels or percent reduction improved ASCVD outcomes. Therefore, this guideline does not recommend their use as performance measures.

o The panel could find no data supporting the routine use of nonstatin drugs combined with statin therapy to reduce further ASCVD events.

o In individuals at higher ASCVD risk receiving the maximum tolerated intensity of statin therapy who continue to have a less-than-anticipated therapeutic response, addition of a nonstatin cholesterol-lowering drug(s) may be considered if the ASCVD risk-reduction benefits outweigh the potential for adverse effects. Preference should be given to drugs shown to reduce ASCVD events in RCTs.

o Attention to adherence to statin and lifestyle therapy and evaluation and treatment of secondary causes that might elevate LDL-C, may address less-than-anticipated responses to a specific statin dosage.

· According to the National Lipid Association, statins should be the initial treatment for all adults with familial hypercholesterolemia. Ezetimibe (Zetia), niacin, and bile acid sequestrants are reasonable treatment options for intensification of therapy, or for those intolerant of statins.

· 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.

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 (Livalo) 1 mg

·      Atorvastatin 10-20 mg

·      Rosuvastatin (Crestor) 5-10 mg

·      Simvastatin 20-40 mg

·      Pravastatin 40-80 mg

·      Lovastatin 40 mg

·      Fluvastatin XL (Lescol XL) 80 mg

·      Fluvastatin 40 mg twice daily

·      Pitavastatin (Livalo) 2-4 mg

·      Atorvastatin 40-80 mg

·      Rosuvastatin (Crestor) 20-40 mg

Approval Criteria

I. Homozygous Familial Hypercholesterolemia (evolocumab only

A. Initiation (< 6 months of therapy)

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

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

2. Evolocumab is being prescribed by or in consultations with one of the following specialties (a. through c.):

a. Cardiologist

b. Lipid Specialist

c. Endocrinologist

3. The member has clinical documentation of homozygous familial hypercholesterolemia, defined as one of the following (a. or b.):

a. Genetic confirmation of two mutant alleles at the LDLR, APOB, OCSK9, or LDLRAP1 gene locus.

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

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

d. The member has a documented untreated LDL-C level > 500 mg/dL

e. The member has a documented treated LDL-C level > 300 mg/dL prior to treatment with a PCSK9 inhibitor

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

A) The member has experienced documented cutaneous or tendon xanthoma before 10 years of age.

B) There is evidence that both of the member’s parents have a diagnosis of heterozygous familial hypercholesterolemia.

4. The prescriber documents that the member will be using evolocumab in combination with a maximally-tolerated statin unless all statins are contraindicated or not tolerated.

5. The prescriber documents that the member will not be using evolocumab in combination with lomitapide (Juxtapid), mipomersen (Kynamro), or another PCSK9 inhibitor.

B. Maintenance (≥ 6 months of therapy)

When a benefit, reauthorization of evolocumab may be approved when all of the following criteria are met (1. through 7.):

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

2. Evolocumab is being prescribed by or in consultations with one of the following specialties (a. through c.):

a. Cardiologist

b. Lipid Specialist

c. Endocrinologist

3. Prior to the start of therapy, the member had clinical documentation of homozygous familial hypercholesterolemia, defined as one of the following (a. or b.):

a. Genetic confirmation of two mutant alleles at the LDLR, APOB, OCSK9, or LDLRAP1 gene locus.

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

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

A) The member has a documented untreated LDL-C level > 500 mg/dL

B) The member has a documented treated LDL-C level > 300 mg/dL prior to treatment with a PCSK9 inhibitor

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

A) The member has experienced documented cutaneous or tendon xanthoma before 10 years of age.

B) There is evidence that both of the member’s parents have a diagnosis of heterozygous familial hypercholesterolemia.

4. The prescriber documents that the member will be using evolocumab in combination with a maximally-tolerated statin unless all statins are contraindicated or not tolerated.

5. The prescriber documents that the member will not be using evolocumab in combination with lomitapide, mipomersen or another PCSK9 inhibitor.

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

7. The member has been adherent to PCSK9 inhibitor therapy as evidenced by claims.

II. Heterozygous Familial Hypercholesterolemia

A. Initiation (< 6 months of therapy)

When a benefit, initial authorization of alirocumab or evolocumab 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. Alirocumab or evolocumab is being prescribed by or in consultations with one of the following specialties (a. through c.):

a. Cardiologist

b. Lipid Specialist

c. Endocrinologist

3. The member has clinical documentation of heterozygous familial hypercholesterolemia, defined as one of the following (a. through c.):

a. Genetic confirmation of one mutant allele at the LDLR, APOB, OCSK9, or LDLRAP1 gene locus.

b. The member has experienced one of the following physical signs of familial hypercholesterolemia (i. through iv.):

i. tendon xanthoma

ii. corneal arcus prior to age 45 years

iii. tuberous xanthoma

iv. xanthelasma

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

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

ii. Definite familial hypercholesterolemia based on the Simon Broome register

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

a. Documentation of an untreated LDL-C ≥ 190 mg/dL

b. Documentation of an untreated LDL-C ≥ 160 mg/dL before age 20 years

5. The member meets both of the following criteria (a. and b.):

a. The member has been previously treated with one of the following as evidenced by pharmacy claims, unless the member is new to plan (i. or ii.):

i. Atorvastatin 40-80 mg and rosuvastatin 20-40 mg for 8 weeks each

ii. Atorvastatin 40-80 mg or rosuvastatin 20-40 mg in combination with ezetimibe for 8 weeks

b. Each previous treatment (see II.A.5.a.) has been ineffective as defined by one of the following (i. through iii.):

i. Failure to achieve ≥ 50% reduction in LDL-C.

ii. LDL-C ≥ 130 mg/dL.

iii. LDL-C ≥ 100 mg/dL in patients with one of the following (A through F):

A) clinically evident coronary heart disease (CHD)

B) atherosclerotic cardiovascular disease

C) diabetes

D) family history of very early CHD defined as one of the following (1 or 2):

1) event in men less than 45 years

2) event in women less than 55 years

E) current smoking

F) lipoprotein (a) ≥ 50 mg/dL

6. The prescriber documents that the member will be using alirocumab or evolocumab in combination with a maximally-tolerated statin.

B. Maintenance (≥ 6 months of therapy)

When a benefit, reauthorization of alirocumab or evolocumab may be approved when all of the following criteria are met (1. through 8.):

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

2. Alirocumab or evolocumab is being prescribed by or in consultations with one of the following specialties (a. through c.):

a. Cardiologist

b. Lipid Specialist

c. Endocrinologist

3. The member has clinical documentation of heterozygous familial hypercholesterolemia, defined as one of the following (a. through c.):

a. Genetic confirmation of one mutant allele at the LDLR, APOB, OCSK9, or LDLRAP1 gene locus.

b. The member has experienced one of the following physical signs of familial hypercholesterolemia (i. through iv.):

i. tendon xanthoma

ii. corneal arcus before age 45 years

iii. tuberous xanthoma

iv. xanthelasma

c. The member met one of the following criteria prior to start of therapy (a. or b.):

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

ii. Definite familial hypercholesterolemia based on the Simon Broome register

4. Prior to the start of therapy, the member met one of the following criteria (a. or b.):

a. Documentation of an untreated LDL-C ≥ 190 mg/dL

b. Documentation of an untreated LDL-C ≥ 160 mg/dL before age 20 years

5. Prior to the start of therapy, the member met both of the following criteria (a. and b.):

a. The member has been previously treated with one of the following as evidenced by pharmacy claims, unless the member is new to plan (i. or ii.):

i. Atorvastatin 40-80 mg and rosuvastatin 20-40 mg for 8 weeks each

ii. Atorvastatin 40-80 mg or rosuvastatin 20-40 mg in combination with ezetimibe for 8 weeks

b. The regimen has been ineffective as defined by one of the following (i. through iii.):

i. Failure to achieve ≥ 50% reduction in LDL-C.

ii. LDL-C ≥ 130 mg/dL.

iii. LDL-C ≥ 100 mg/dL in patients with one of the following (A through F):

A) clinically evident coronary heart disease (CHD)

B) atherosclerotic cardiovascular disease

C) diabetes

D) family history of very early CHD defined as one of the following (1 or 2):

1) event in men less than 45 years

2) event in women less than 55 years

E) current smoking

F) lipoprotein (a) ≥ 50 mg/dL

6. The prescriber documents that the member will be using alirocumab or evolocumab in combination with a maximally-tolerated statin.

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

a. The member has experienced at least a 50% reduction in LDL-C from baseline.

b. If the member had a baseline LDL-C of > 130 mg/dL, the member has a documented LDL-C ≤ 130 mg/dL.

8. The member has been adherent to PCSK9 inhibitor therapy as evidenced by claims.

III. Hypercholesterolemia, ASCVD

A. Initiation (< 6 months of therapy)

When a benefit, initial authorization of alirocumab or evolocumab 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. Alirocumab or evolocumab is being prescribed by or in consultations with one of the following specialties (a. through c.):

a. Cardiologist

b. Lipid Specialist

c. Endocrinologist

3. The member has a documented diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) as defined by one 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

4. The member meets both of the following criteria (a. and b.):

a. The member has been previously treated with one of the following as evidenced by pharmacy claims, unless the member is new to plan (i. or ii.):

i. Atorvastatin 40-80 mg and rosuvastatin 20-40 mg for 8 weeks each

ii. Atorvastatin 40-80 mg or rosuvastatin 20-40 mg in combination with ezetimibe for 8 weeks

b. Each regimen has been ineffective in achieving an LDL-C < 100 mg/dL.

5. The prescriber documents that the member will be using alirocumab or evolocumab in combination with a maximally-tolerated statin.

6. The prescriber documents that the member is currently enrolled in a lipid or disease management clinic.

B. Maintenance (≥ 6 months of therapy)

When a benefit, reauthorization of alirocumab or evolocumab may be approved when all of the following criteria are met (1. through 7.):

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

2. Alirocumab or evolocumab is being prescribed by or in consultations with one of the following specialties (a. through c.):

a. Cardiologist

b. Lipid Specialist

c. Endocrinologist

3. The member has a documented diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) as defined by one 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

4. Prior to start of therapy, the member met both of the following criteria (a. and b.):

a. The member has been previously treated with one of the following as evidenced by pharmacy claims, unless the member is new to plan (i. or ii.):

i. Atorvastatin 40-80 mg and rosuvastatin 20-40 mg for 8 weeks each

ii. Atorvastatin 40-80 mg or rosuvastatin 20-40 mg in combination with ezetimibe for 8 weeks

b. Each regimen has been ineffective in achieving an LDL-C < 100 mg/dL.

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

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

b. If the member has a documented LDL-C ≤ 100 mg/dL.

6. The member has been adherent to PCSK9 inhibitor therapy as evidenced by claims.

7. The prescriber documents that the member is currently enrolled in a lipid or disease management clinic.

· Use of alirocumab or evolocumab for disease states outside of its FDA-approved indications should be denied based on the lack of clinical data to support its effectiveness and safety in other conditions.

· For 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.

Quantity Level Limitation

Members who meet the above clinical criteria will be eligible for approval of 2 syringes/autoinjectors per 28 days or 6 syringes/autoinjectors per 84 days (if benefit allows). Authorization of additional evolocumab quantities (3 syringes/autoinjectors per 30 days or 9 syringes/autoinjectors per 90 days (if benefit allows)) may be considered for approval if the member meets all of the following criteria (A):

A. The member has a diagnosis of homozygous familial hypercholesterolemia.

Duration of Authorization

Initiation: If approved, a 6 month authorization may be granted.

Maintenance: If approved, a 12 month authorization may be granted.

References

1. Stone, N. J., Robinson, J., Lichtenstein, A. H., et al. 2013 ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation 2013. Retrieved from: http://circ.ahajournals.org.

2. Goldberg, A. C., Hopkins, P. N., Toth, P. P., et al. Familial hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients. Clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J. of Clinical Lipidology 2011 Volume 5, Number 3S.

3. Praluent [prescribing information]. Tarrytown, NJ: Sanofi-Aventis and Regeneron Pharmaceuticals, Inc.; July 2015.

4. Repatha [prescribing information]. Thousand Oaks, CA: Amgen Inc.; August 2015.

5. DRUGDEX System (Micromedex 2.0). Greenwood Village, CO: Truven Health Analytics; c1974-2013. Accessed 7/27/2015.