Prior Auth Protocol

FDA Approved Indications:

As adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous (He) familial hypercholesterolemia (FH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-cholesterol

Health Net Approved Indications and Usage Guidelines:

Diagnosis of Heterozygous Familial Hypercholesterolemia based on documentation (e.g., medical records, chart notes, laboratory values) of LDL level suggestive of familial hypercholesterolemia (e.g., Adults: baseline LDL >190 mg/dL; Children less than 16 years of age: baseline LDL >155 mg/dL)

OR

Diagnosis of hypercholesterolemia with history of clinical atherosclerotic cardiovascular disease defined as:
- LDL≥130 mg/dL

AND

Documented history of one of the following:

Acute coronary syndromes
Myocardial Infarction
Stable or unstable angina
Coronary or other arterial revascularization (e.g., percutaneous coronary intervention or coronary artery bypass graft surgery)
Stroke
Peripheral artery disease presumed to be of atherosclerotic origin
Transient ischemic attack (TIA)
Clinically significant coronary heart disease (CHD) diagnosed by invasive or noninvasive testing (such as coronary angiography, stress test using treadmill, stress echocardiography, or nuclear imaging)
Carotid artery occlusion >50% without symptoms
Renal artery stenosis or renal artery stent procedure
AND

Prescribed by or in consultation with a Cardiologist, Endocrinologist, or lipid specialist

AND

Documentation of concomitant therapy with Zetia in combination with high-intensity statin therapy (atorvastatin 40mg or Crestor^R 20 mg or greater) or Vytorin at simvastatin doses of at least 40 mg for a minimum of two months

OR

Clinically significant adverse effects to atorvastatin (≥40 mg), Crestor (≥20 mg) and documentation of concomitant therapy with Zetia in combination with maximally tolerated statin therapy [see General Information section] for a minimum of two months

OR

For patients not on statin therapy (statin intolerant):
- Documentation of concomitant therapy with Zetia

AND

Documentation of one of the following:

1. Statin re-challenge with at least the lowest dose of at least two of the following: pravastatin 10 mg, fluvastatin 20 mg, or rosuvastatin 5 mg, [see General Information section]
AND
At least intermittent or alternate dosing frequency (e.g., 1 to 3 times weekly) has been attempted
2. History of rhabdomyolysis
3. History of two consecutive abnormal liver function tests (LFT) greater than three times the upper limit of normal (ULN) and experienced symptoms suggesting hepatotoxicity (e.g., jaundice, dark-colored urine, light or clay-colored stools) while taking statin

FOR PRALUENT 150 MG REQUESTS:

Failure to achieve LDL <70 after 8 weeks of therapy with Praluent 75 mg

REAUTHORIZATION REQUESTS:

Documentation of LDL reduction while on PCSK9 therapy defined as at least 25% LDL reduction from baseline or LDL<70mg/dL for high risk patients or LDL <100mg/DL for moderate risk patients

AND

Confirmation of continued statin therapy at the maximally tolerated dose [see general information] with demonstrated adherence

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

FDA advisory briefing documents discuss the questionable determination of statin intolerance, stating: "many patients who are not able to take statins are not truly intolerant of the pharmacological class. As demonstrated in this program (ODYSSEY-ALTERNATIVE), when patients who met what was thought to be a rigorous clinical definition of statin intolerance were randomly assigned to receive atorvastatin 20 mg daily in a blinded fashion, 70% completed a 24-week trial. Preceding the randomized portion of this trial, 361 "statin-intolerant" patients entered a single-blind placebo run-in period, during which 23 (49%) of 47 run-in failures discontinued because of skeletal muscle-related adverse events that occurred while taking placebo."
Maximally tolerated statin dose is defined as the inability to titrate to one of the following statin dosages due to skeletal muscle or hepatic related symptoms, concomitant medications, or medical conditions: rosuvastatin 20 mg, atorvastatin 40 mg, simvastatin 40 mg.
The 2013 ACC/AHA treatment guidelines include the following conditions as clinical ASCVD: acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin.
Baseline LDL prior to lipid lowering therapy should be used to satisfy the diagnostic criteria for Familial Hypercholesterolemia.
Patients should remain on concomitant therapy with a statin if tolerated due to the established long term cardiovascular benefits.
Patients with high risk of ASCVD include the following:
- History of clinical atherosclerotic cardiovascular disease (as defined in section II)
- Diabetes with an estimated 10-year ASCVD risk ≥7.5% for adults 40-75 years of age
- Untreated LDL ≥190 mg/dL
Patients with moderate risk of ASCVD include the following:
- Diabetes with an estimated 10-year ASCVD risk <7.5% for adults 40-75 years of age
- Estimated 10-year ASCVD risk ≥5% for adults 40-75 years of age
The calculator for the 10-year ASCVD risk estimator can be found here: http://tools.cardiosource.org/ASCVD-Risk-Estimator/. Information needed to complete the ASCVD Risk Estimator include: gender, race (white, African American, other), systolic blood pressure, diabetes, age, total cholesterol, HDL-Cholesterol, treatment for hypertension, current smoker
Statin re-challenge should be performed with pravastatin, fluvastatin or rosuvastatin due to their hydrophilicity which appear to produce less intrinsic muscle toxicity and fewer drug interactions compared to other statins. Re-challenge requires slow titration with lower intensity statins to titrate up to the patients maximally tolerated statin dose with the goal of high-intensity statin use.
According to the 2013 AHA/ACC lipid guidelines, rhabdomyolysis is a very rare condition. In adults selected for participation in clinical trials of statin therapy, rhabdomyolysis occurred rarely (<0.06% over a mean 4.8 to 5.1 year treatment period). If rhabdomyolysis occurs, documentation via creatine kinase (CK) levels above >10x ULN is required.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Vytorin (ezetimibe/simvastatin)	10/40 mg PO QD	10/40 mg PO QD (Use of the 10/80 mg dose is restricted to patients who have been taking simvastatin 80 mg for 12 months or more without evidence of muscle toxicity)
atorvastatin (Lipitor)	40 mg PO QD	80 mg PO QD
Crestor (rosuvastatin)	5 - 40 mg PO QD	40 mg PO QD
Repatha	140 mg SC Q2 wks or 420 mg SC once monthly	420 mg once monthly

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Praluent 75 mg	75 mg SC once every 2 weeks	6 months Reauthorization requests require confirmation of continued statin therapy at the maximally tolerated dose with demonstrated adherence (unless contraindicated or statin intolerant) AND documentation of LDL reduction while on Praluent therapy (defined as at least 25% LDL reduction from baseline or LDL<70mg/dL for high risk patients or LDL <100mg/DL for medium risk patients) Continued treatment will be approved for 1 year.
Praluent 150 mg	If response to 75 mg is inadequate, dose may be increased to 150 mg Requests for Praluent 150 mg require documentation that patient is unable to achieve a LDL <70 after 8 weeks of therapy with Praluent 75 mg	6 months Reauthorization requests require confirmation of continued statin therapy at the maximally tolerated dose with demonstrated adherence (unless contraindicated or statin intolerant) AND documentation of LDL reduction while on Praluent therapy (defined as at least 25% LDL reduction from baseline or LDL<70mg/dL for high risk patients or LDL <100mg/DL for medium risk patients). Continued treatment will be approved for 1 year.

Product Availability:

Single-use pre-filled pen, syringe: 75 mg/mL, 150 mg/mL

References:

1. Food and Drug Administration Center for Drug Evaluation and Research: The Endocrinology and Metabolic Drugs Advisory Committee Meeting Briefing Document BLA 125559 - Praluent (alirocumab) injection. June 9, 2015. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM449865.pdf. Accessed: June 9, 2015.

2. Stone NJ, Robinson JG, Lichtenstein AH, 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. 2014 June 24; 129[suppl 2]: S1-S45.

3. Moriarty PM, Jacobsen TA, Bruckert E, et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: Design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial.

4. Praluent [Prescribing Information]. Bridgewater, NJ; Sanofi Aventis and Regeneron Pharmaceuticals: July 2015.

5. Hopkins PN, Toth PP, Ballantyne CM, et al. Familial Hypercholesterolemias: Prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. Journal of Clinical Lipidology. 2011. 5; S9-S17.