ph-991045
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Homozygous Familial Hpercholesterolemia Agents (HoFH) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-991045

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

Homozygous Familial Hypercholesterolemia Agents Prior Authorization with Quantity Limit

TARGET AGENT(S)

Juxtapid® (lomitapide)

Brand (generic)

GPI

Multisource Code

Quantity Limit (per day or as listed)

Juxtapid (lomitapide)

5 mg capsule

39480050200120

M, N, O, or Y

1 capsule

10 mg capsule

39480050200130

M, N, O, or Y

1 capsule

20 mg capsule

39480050200140

M, N, O, or Y

1 capsule

30 mg capsule

39480050200150

M, N, O, or Y

1 capsule

40 mg capsule

39480050200160

M, N, O, or Y

1 capsule

60 mg capsule

39480050200170

M, N, O, or Y

1 capsule

PRIOR AUTHORIZATION CRITERIA FOR APPROVAL

Initial Evaluation

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

  1. ONE of the following:
    1. The patient has the diagnosis of homozygous familial hypercholesterolemia (HoFH) and ALL of the following:
      1. The patient has a confirmed diagnosis of homozygous familial hypercholesterolemia (HoFH), through ONE of the following:
        1. Genetic confirmation of two mutant alleles at the LDLR, Apo-B, PCSK9, ARH adaptor protein 1/LDLRAP1 gene locus

OR

        1. History of untreated LDL-C >500 mg/dL (>13 mmol/L) or treated LDL-C ≥300 mg/dL (≥7.76 mmol/L) with ONE of the following:
          1. The patient had cutaneous or tendon xanthoma before age 10 years

OR

          1. Untreated elevated cholesterol levels consistent with heterozygous FH in both parents [untreated LDL-C >190 mg/dL (>4.9 mmol/L) or untreated total cholesterol greater than 290 mg/dL (>7.5 mmol/L)]

AND

      1. ONE of the following:
        1. The patient is on a maximally tolerated statin containing lipid-lowering regimen (i.e., rosuvastatin in combination with ezetimibe OR atorvastatin in combination with ezetimibe)

OR

        1. The patient has an intolerance or hypersensitivity to ALL of these therapies (i.e., rosuvastatin in combination with ezetimibe AND atorvastatin in combination with ezetimibe)

OR

        1. The patient has an FDA labeled contraindication to ALL of these therapies (i.e., rosuvastatin in combination with ezetimibe AND atorvastatin in combination with ezetimibe) 

AND

      1. ONE of the following:
        1. The patient has tried with adherence for at least 3 months and had an inadequate response to a PCSK9 inhibitor (e.g., Repatha, Praluent)

OR

        1. The patient has an intolerance or hypersensitivity to ALL PCSK9 inhibitors

OR

        1. The patient has an FDA labeled contraindication to ALL PCSK9 inhibitors

AND

      1. The patient is taking daily vitamin E, linoleic acid, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) supplements

OR

    1. The patient has another FDA approved indication for the requested agent

OR

    1. The patient has another indication that is supported in compendia (DrugDex 1 or 2a level of evidence, AHFS) for the requested agent and route of administration

          AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, endocrinologist, lipid specialist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

Length of Approval: 12 months

Renewal Evaluation

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

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process

AND

  1. The patient has had clinical benefit with the requested agent

AND

  1. If the patient’s diagnosis is homozygous familial hypercholesterolemia, BOTH of the following:
    1. ONE of the following:
      1. The patient is on a maximally tolerated statin containing lipid-lowering regimen (i.e., rosuvastatin in combination with ezetimibe OR atorvastatin in combination with ezetimibe)

                                    OR

      1. The patient has an intolerance or hypersensitivity to ALL of these therapies (i.e., rosuvastatin in combination with ezetimibe AND atorvastatin in combination with ezetimibe) 

OR

      1. The patient has an FDA labeled contraindication to ALL of these therapies (i.e., rosuvastatin in combination with ezetimibe AND atorvastatin in combination with ezetimibe)

AND

    1. The patient is taking daily vitamin E, linoleic acid, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) supplements

AND

  1. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, endocrinologist, lipid specialist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

 

Length of approval: 12 months

 

FDA APPROVED INDICATIONS AND DOSAGE1

Agent(s)

Indication(s)

Dosage

Juxtapid®

(lomitapide)

Capsule

Adjunct therapy to a low-fat diet and other lipid lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B) and non-high density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

Limitations of Use:

  • The safety and effectiveness of Juxtapid have not been established in patients with hypercholesterolemia who do not have HoFH, including those with heterozygous familial hypercholesterolemia (HeFH)
  • The effect of Juxtapid on cardiovascular morbidity and mortality has not been determined
  • The recommended starting dose is 5 mg/day, (titrate dose based on acceptable safety/tolerability) after at least 2 weeks increase to 10 mg/day, dose then can be increased every 4 weeks to 20 mg/day, 40 mg/day, and up to the maximum recommended dose of 60 mg/day orally
  • Patients with end-stage renal disease on dialysis or with baseline mild hepatic impairment should not exceed 40 mg daily
  • Take with glass of water, without food, at least 2 hours after evening meal 
  • Due to reduced absorption of fat-soluble vitamins/fatty acids: Take daily vitamin E, linoleic acid, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) supplements

CLINICAL RATIONALE

Guidelines advise that diagnosis of HoFH can be made on the basis of genetic or clinical criteria. Genetic confirmation of the HoFH includes confirmation of two mutant alleles at the LDL-R, APOB, PCSK9, or LDLRAP1 genes. While genetic testing may provide a definitive diagnosis of HoFH, it is recognized that in some patients, genetic confirmation remains elusive, despite exhaustive investigation; indeed, the existence of additional FH genes cannot be excluded. Historically, HoFH has been most commonly diagnosed on the basis of either an untreated LDL-C plasma concentration >13 mmol/L (>500 mg/dL), or a treated LDL-C concentration of ≥8 mmol/L (≥300 mg/dL), accompanied by the presence of cutaneous or tendon xanthomas before the age of 10 years, or the presence of untreated elevated LDL-C levels consistent with HeFH in both parents.2,3

Guidelines

The American Heart Association released a scientific statement for familial hypercholesterolemia that recommended lomitapide may be considered in HoFH patients once a four-drug combination is needed (after rosuvastatin or atorvastatin + ezetimibe + one of the following: PCSK9 inhibitors or colesevelam or other bile acid sequestrant, or niacin combination has been taken by an adherent patient for 3 months and LDL-C is still above goal).5

The European Atherosclerosis Society (EAS) 2014 Consensus Panel clinical guidelines on HoFH state “Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centers for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide for HoFH. Given the severity of ACVD, regular follow-up is recommended, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary.2

The American Association of Clinical Endocrinologists (AACE) 2017 guidelines state that lomitapide may be useful for individuals with HoFH not responsive to PCSK9 therapy.6

The National Organization for Rare Disorders (NORD) states that patients with HoFH are started on statins as soon as the diagnosis is made but these treatments may not be effective alone. Patients with HoFH often require additional treatment strategies including lomitapide and PCSK9 agents. Additional options include LDL apheresis or liver transplantation.4

Safety

Lomitapide has a boxed warning for risk of hepatotoxicity.  It can cause elevations in liver enzymes and increase hepatic fat (steatosis).  It is recommended to measure ALT, AST, alkaline phosphatase, and total bilirubin prior to initiating therapy and AST and ALT regularly during therapy.  Discontinue for clinically significant liver toxicity.1

Lomitapide also has a REMS program to ensure proper prescribing of the specific agent.1

Contraindications for lomitapide:1

  • Pregnancy
  • Concomitant use of moderate or strong CYP3A4 inhibitors

Moderate CYP3A4 inhibitors

Diltiazem

Fluconazole

Erythromycin

Strong CYP3A4

Itraconazole or ketoconazole

Erythromycin/clarithromycin

HIV protease inhibitors

nefazodone

  • Moderate to severe hepatic impairment or active liver disease including unexplained persistent abnormal liver function tests

REFERENCES

  1. Juxtapid prescribing information.  Aegerion Pharmaceuticals, Inc.  Cambridge, MA.  September 2020.
  2. 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. European Heart Journal. 2014; 35(32):2146-2157.  https://doi.org/10.1093/eurheartj/ehu274 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: http://www.ncbi.nlm.nih.gov/books/NBK53822/
  3. National Organization for Rare Disorders (NORD). Physician guide to Homozygous Familial Hypercholesterolemia (HoFH). https://rarediseases.org/physician-guide/homozygous-familial-hypercholesterolemia-hofh/
  4. American Heart Association Scientific Statement: The Agenda for Familial Hypercholesterolemia. Circulation 2015; 132: 2167-2192.
  5. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular disease. AACE 2017 Guidelines. Endocrine Practice. 2017 Apr; 23 (Suppl 2):1-87. doi: 10.4158/EP171764.APPGL. PMID: 28437620.

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 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.

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