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Date Printed: August 21, 2017: 07:40 PM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J0000-76

Original Effective Date: 09/15/08

Reviewed: 06/14/17

Revised: 07/15/17

Subject: Oral Therapy for Gaucher Disease

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Gaucher disease is characterized by a deficiency of ß-glucocerebrosidase activity, resulting in accumulation of glucocerebrosidase in tissue macrophages which become engorged and are typically found in the liver, spleen and bone marrow and occasionally in lung, kidney and intestine. Secondary hematologic sequelae include severe anemia and thrombocytopenia in addition to the characteristic progressive hepatosplenomegaly, skeletal complications, including osteonecrosis and osteopenia, with secondary pathological fractures. Some forms of Gaucher disease cause significant disability and can be fatal.

Symptoms of Gaucher disease include fatigue, prolonged bleeding, easy bruising, bone pain, and pathological fractures. Signs of Gaucher disease include an enlarged spleen and liver, severe anemia, abnormal pigmentation, bone lesions, and occasionally lung dysfunction. In more severe cases, toxic levels of glycolipids accumulate in the nervous system, causing neuronal loss. Most cases have no neurological involvement and are not diagnosed until adulthood (Type I). The clinical severity of type 1 is variable; some individuals never become symptomatic, and are only diagnosed after death (from other causes) upon autopsy. Other individuals with type 1 disease develop crippling skeletal symptoms during childhood.

The preferred treatment of type 1 Gaucher disease is enzyme replacement therapy (e.g., imiglucerase [Cerezyme®], velaglucerase [Vpriv™], or taliglucerase [Elelyso™]), which increases the degradation of glucocerebroside in macrophages with resultant reduction in the manifestations of Gaucher disease. However, oral treatment is available with Eliglustat (Cerdelga®) and Miglustat (Zavesca®).

Eliglustat is an oral glucosylceramide synthase inhibitor indicated for the long-term treatment of adult patients with Gaucher disease type 1 (GD1). Unlike enzyme replacement therapies, which break down fatty deposits that build up in cells of patients with Gaucher disease, eliglustat slows the accumulation of the fatty deposits by inhibiting the metabolic process that forms them. Although ease of oral administration provides substantial benefit over intravenous enzyme replacement therapy, eliglustat use is somewhat limited by cytochrome P450 (CYP450) 2D6 genotype. Eliglustat is primarily metabolized via CYP2D6 and, to a lesser extent, CYP3A. Patient selection should take into account CYP2D6 metabolizer status, as established by a FDA-cleared test. Patients who are CYP2D6 ultra-rapid metabolizers may not achieve therapeutic concentrations of eliglustat. Poor metabolizers require dosage reduction. In addition, depending on the patient's CYP2D6 metabolizer status, concomitant administration of some CYP2D6 and CYP3A inhibitors may be contraindicated or require dosage adjustment to reduce the risk of potentially significant ECG changes.

Miglustat is approved for the management of mild to moderate nonneuronopathic (type1) Gaucher disease in individuals for whom enzyme replacement therapy is unsuitable (e.g., because of allergy, hypersensitivity, poor venous access). Unlike enzyme replacement therapy, miglustat inhibits the formation of the substrate (glucocerebroside) for the deficient enzyme (substrate reduction therapy). Because all individuals with type 1 Gaucher disease have some level of residual glucocerebrosidase activity, reduction in the amount of substrate allows the residual activity of the deficient enzyme to be more effective, decreasing glucocerebroside accumulation in macrophages. Of note, the safety and efficacy of miglustat have not been established in individuals with severe type 1 Gaucher disease (i.e., hemoglobin less than 9 g/dL, platelet count less than 50,000/mm3, or active bone disease).

POSITION STATEMENT:

Initiation of eliglustat (Cerdelga) or miglustat (Zavesca) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with Type 1 Gaucher disease confirmed by either of the following:

a. Genotype testing indicating a mutation of two alleles of the glucocerebrosidase genome – laboratory documentation must be provided

b. Glucocerebrosidase activity deficiency in the white blood cells/skin fibroblasts – laboratory documentation must be provided

2. Drug will be used as monotherapy (i.e., not in combination with eliglustat [Cerdelga], miglustat [Zavesca], imiglucerase [Cerezyme], alglucerase [Ceredase], velaglucerase [Vpriv], or taliglucerase [Elelyso])

3. Member meets ONE of the following:

a. Eliglustat requests: Member has undergone an FDA-approved test and been proven to be one of the following:

i. Extensive CYP2D6 metabolizer – laboratory documentation must be provided

ii. Intermediate CYP2D6 metabolizer – laboratory documentation must be provided

iii. Poor CYP2D6 metabolizer – laboratory documentation must be provided

b. Miglustat requests: Intravenous enzyme replacement therapy is not a therapeutic option due to one or more of the following:

i. Allergy – documentation from the medical record must be provided

ii. Hypersensitivity – documentation from the medical record must be provided

iii. Poor venous access – documentation from the medical record must be provided

4. Member is currently receiving enzyme replacement therapy OR has one or more of the following conditions:

a. Hemoglobin less than 1.0 g/dL below lower limit of normal for age and gender

b. Thrombocytopenia (platelet count less than 120,000)

c. Clinically significant hepatomegaly

d. Clinically significant splenomegaly

e. Evidence of bone disease other than Erlenmeyer flask deformity or mild osteopenia.

5. Member is 18 years of age or older

6. Dose does not exceed:

a. Eliglustat:

i. Extensive CYP2D6 metabolizer: 84 mg twice daily

ii. Intermediate CYP2D6 metabolizer: 84 mg twice daily

iii. Poor CYP2D6 metazolizer: 84 mg once daily

b. Miglustat: 300 mg/day

Approval duration: 1 year

Continuation of eliglustat (Cerdelga) or Miglustat (Zavesca) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Florida Blue or another health plan in the past two years for treatment of Type 1 Gaucher disease, OR the member has previously met all indication-specific criteria

2. Member demonstrates a benefical response to treatment

3. Drug will be used as monotherapy (i.e., not in combination with eliglustat [Cerdelga], miglustat [Zavesca], imiglucerase [Cerezyme], alglucerase [Ceredase], velaglucerase [Vpriv], or taliglucerase [Elelyso])

4. Dose does not exceed:

a. Eliglustat:

i. Extensive CYP2D6 metabolizer: 84 mg twice daily

ii. Intermediate CYP2D6 metabolizer: 84 mg twice daily

iii. Poor CYP2D6 metazolizer: 84 mg once daily

b. Miglustat: 300 mg/day

Approval duration: 1 year

Miglustat meets the definition of medical necessity when used for treatment of the following designated Orphan Drug indication:

1. Type C Niemann-Pick disease AND dose does not exceed 200 mg three times daily

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-Approved:

• Eliglustat: 84 mg orally twice daily

• Miglustat: 100 mg orally three times daily

Dosage Adjustments

• Eliglustat:

o CYP2D6 extensive metabolizers (EMs): 84 mg/dose PO twice daily.

o CYP2D6 intermediate metabolizers (IMs): 84 mg/dose PO twice daily.

o CYP2D6 poor metabolizers (PMs): 84 mg/dose PO once daily.

• Miglustat:

o Renal Impairment:

o Mild impairment (CrCl 50-70 ml/min): Reduce dose to 100 mg twice daily

o Moderate impairment (CrCl 30-50 ml/min): Reduce dose to 100 mg daily

o Severe impairment (CrCl less than 30 ml/min): Avoid use

o Adverse Reactions (e.g., diarrhea or tremor): Reduce dose to 100 mg once or twice daily.

Drug Availability:

• Eliglustat is available as an 84 mg capsule

• Miglustat is available as a 100 mg hard gelatin capsule

PRECAUTIONS:

CONTRAINDICATIONS

• Eliglustat:

o CYP2D6 EMs and IMs taking a strong or moderate CYP2D6 inhibitor with a strong or moderate CYP3A inhibitor

o CYP2D6 IMs and PMs taking a strong CYP3A inhibitor

• Miglustat: None

WARNINGS

• Eliglustat:

o ECG Changes and Potential for Cardiac Arrhythmias

• Miglustat:

o Peripheral Neuropathy: Members should undergo baseline and repeat neurological evaluations at approximately 6-month intervals. Development of symptoms such as numbness and tingling require careful re-assessment of risk/benefit of miglustat therapy and treatment discontinuation may be considered.

o Gastrointestinal: Diarrhea and weight loss were common in clinical studies. Members with persistent gastrointestinal events should be evaluated to determine if significant underlying gastrointestinal disease is present.

o Tremor: In clinical studies, tremor was observed, usually occurring within the first month of therapy and in many cases resolved between 1 to 3 months during treatment. Dose reduction may ameliorate tremor usually within days, but discontinuation may sometimes be required.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J8499

Prescription drug, oral, non-chemotherapeutic, NOS

ICD-10 Diagnoses Codes That Support Medical Necessity:

E75.22

Gaucher disease

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

Medicare Part D: Florida Blue has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

Gaucher disease: Is a familial disorder of lipid metabolism resulting in an accumulation of abnormal glucocerebrosides in reticuloendothelial cells, and manifested clinically by hepatosplenomegaly, skin pigmentation, skeletal lesions, and pingueculae.

Type C Niemann-Pick Disease: Niemann-pick disease refers to a group of inherited diseases in which lipids collect in the cells of the spleen, liver, and brain. There are four most commonly recognized forms of the disease: Types A, B, C, and D. Type C occurs when the body cannot properly break down cholesterol and other lipids. It usually affects school-aged children.

RELATED GUIDELINES:

Intravenous Enzyme Replacement Therapy for Gaucher Disease, 09-J0000-41

OTHER:

None applicable.

REFERENCES:

  1. Clinical Pharmacology. [database online]. Tampa, FL: Gold Standard, Inc.; 2014. URL. www.Clinicalpharamcology-ip.com Accessed 4/28/2017.
  2. Ingenix ICD-9-CM for Physicians-Volumes 1 & 2, Expert 2014.
  3. Micromedex Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 4/28/17.
  4. Miglustat. In McEvoy GK, editor. AHFS drug information 2014 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2014 [cited 2014 Apr 28].
  5. Zavesca (miglustat) [package insert]. Actelion Pharmaceuticals US. Inc. South San Francisco (CA): February 2014.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 06/14/17.

GUIDELINE UPDATE INFORMATION:

09/15/08

New Medical Coverage Guideline.

10/15/09

Review and revision; consisting of adding definition and updating references.

12/15/10

Review and revision; consisting of updating coding and references.

12/15/11

Review and revision to guideline; consisting of updating precautions and references.

12/15/12

Review and revision to guideline; consisting of revising description, position statement, dosage administration, and precaution sections; added contraindications section.

07/15/13

Review and revision to guideline; consisting of revising position statement to include approval duration and updating program exceptions and references.

07/15/14

Review and revision to guideline; consisting of reformatting position statement, updated dosage/administration section, references, and coding.

11/15/14

Revision to guideline; consisting of description, position statement, dosage/administration, precautions/warnings, references.

01/15/15

Revision to guideline; consisting of updating position statement.

07/15/15

Review and revision to guidelines; consisting of updating description, position statement, coding, references.

11/01/15

Revision: ICD-9 Codes deleted.

01/15/16

Revision to guideline; consisting of updating position statement.

07/15/16

Review and revision to guideline; consisting of updating position statement.

07/15/17

Review and revision to guideline; consisting of updating position statement and description.

Date Printed: August 21, 2017: 07:40 PM