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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-J0000-41

Original Effective Date: 04/15/02

Reviewed: 06/14/17

Revised: 07/15/17

Subject: Intravenous Enzyme Replacement 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.

           
Position Statement Dosage/ Administration 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.

There are three clinical subtypes of Gaucher disease: type 1, type 2, and type 3. Type 1 (or non-neuronopathic) is the most common and symptoms being early in life or in adulthood. Most cases have no neurological involvement and are not diagnosed until adulthood. The clinical severity of type 1 is variable with some individuals never becoming symptomatic and others developing crippling skeletal symptoms during childhood. In type 2 Gaucher disease (acute infantile neuropathic Gaucher disease), liver and spleen enlargement are apparent by 3 months of age and individuals usually die before the age of two. Last, type 3 (or chronic neuronopathic Gaucher disease), liver and spleen enlargement varies and signs of brain involvement such as seizures gradually become apparent. Major symptoms also include skeletal irregularities, eye movement disorders, respiratory problems and blood disorders.

The preferred treatment of type 1 Gaucher disease is enzyme replacement therapy (e.g., imiglucerase [Cerezyme®], alglucerase [Ceredase®], 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®). Enzyme replacement therapy may ameliorate visceromegaly and hematologic abnormalities in type 2 Gaucher disease. However, the recombinant enzyme does not cross the blood brain barrier and there is no evidence that enzyme replacement therapy has reversed, stabilized, or slowed the progression of neurological involvement. Enzyme replacement therapy is also used in Gaucher disease type 3.

Alglucerase (Ceredase) was the first drug approved by the U.S. Food and Drug Administration (FDA) for treatment of type 1 Gaucher disease. It was manufactured from human placental tissue and has since been withdrawn from the market due to the approval of similar drugs made with recombinant DNA technology.

Imiglucerase (Cerezyme) is an analogue of the human enzyme ß-glucocerebrosidase. It is FDA approved for long-term enzyme replacement therapy (ERT) for pediatric and adult patients with a confirmed diagnosis of type 1 Gaucher disease that results in anemia, thrombocytopenia, bone disease, hepatomegaly, or splenomegaly.

Velaglucerase alfa (Vpriv) and taliglucerase alfa (Elelyso) are enzymes created by gene activation technology in human fibroblast cells. Both velaglucerase alfa and taliglucerase alfa are FDA approved for long-term ERT for patients with type 1 Gaucher disease and have orphan drug designation for this same indication.

POSITION STATEMENT:

Initiation of imiglucerase (Cerezyme), velaglucerase (Vpriv), or taliglucerase (Elelyso) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with ONE of the following:

a. Type 1 Gaucher disease confirmed by either of the following:

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

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

b. Type 3 Gaucher disease confirmed by BOTH of the following:

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

ii. Neurologic manifestations consistent with Type 3 Gaucher disease (e.g., abnormal eye movement, seizures) – documentation from the medical record 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. Younger than 18 years of age AND has one or more of the following:

i. Abdominal or bone pain

ii. Documented growth failure not associated with other conditions

iii. Cachexia

iv. Exertional limitations or fatigue

v. Evidence of bone disease

vi. Hemoglobin less than 2 g/dL below lower limit of normal for age and gender

vii. Thrombocytopenia (platelet count less than 60,000)

viii. Documented abnormal bleeding episode

b. 18 years of age and older AND has ONE OR MORE of the following:

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

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

iii. Clinically significant hepatomegaly

iv. Clinically significant splenomegaly

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

4. Dose does not exceed 60 units/kg IV every 2 weeks

Approval duration: 1 year

Continuation imiglucerase (Cerezyme), velaglucerase (Vpriv), or taliglucerase (Elelyso) 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 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 60 units/kg IV every 2 weeks

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.

Table 2

FDA-Approved Indications and Recommended Dosing

Drug

FDA-approved indication

Initial Dose

Usual Dosage

Comments

Imiglucerase (Cerezyme)

Long-term ERT in Type 1 Gaucher disease

2.5 units/kg
three times weekly to 60 units/kg
every 2 weeks

60 units/kg IV
every 2 weeks

Administer over 1-2 hours

Velaglucerase alfa (Vpriv)

Long-term ERT in Type 1 Gaucher disease

60 units/kg IV
every 2 weeks

60 units/kg IV
every 2 weeks

• Administer over 1 hour

• Members currently treated with a stable dose of imiglucerase may be switched to the same dose of velaglucerase

Taliglucerase alfa

(Elelyso)

Long-term ERT in Type 1 Gaucher disease

60 units/kg IV
every 2 weeks

60 units/kg IV
every 2 weeks

• Administer over 1-2 hours

• Members currently treated with a stable dose of imiglucerase may be switched to the same dose of taliglucerase

ERT, Enzyme replacement therapy

Table 3

Drug Availability

Imiglucerase (Cerezyme)

• 200 unit powder for injection

• 400 unit powder for injection

Velaglucerase (Vpriv)

400 unit powder for injection

Taliglucerase (Elelyso)

200 unit powder for injection

Dosage Adjustment: Specific guidelines for dosage adjustments in hepatic or renal impairment are not available; it appears that no dosage adjustments are needed.

PRECAUTIONS:

CONTRAINDICATIONS:

There are no known contraindications to therapy with imiglucerase, velaglucerase and taliglucerase; however, they should be used with caution in members with a known hypersensitivity to the product.

Allergic and Infusion Reactions: Infusion-related reactions (including allergic reactions) have been observed following administration of enzyme replacement therapy. The majority of the reactions were mild and dissipated over time. Slowing the infusion rate or pretreatment with antihistamines and/or corticosteroids may prevent subsequent reactions in those cases where symptomatic treatment was required.

Children

• The safe and effective use of imiglucerase has been established in children and adolescents age 2 to 16 years.

• The safe and effective use of velaglucerase has been established in children over the age of 4 years.

• The safety and efficacy of taliglucerase has been established in children 4 years of age and older.

Pregnancy and Lactation

• Imiglucerase is classified as Pregnancy Category C; there are no adequate and well-controlled studies in pregnant women.

• Taliglucerase and velaglucerase are classified as Pregnancy Category B; although there are no adequate and well-controlled studies in pregnant women, reproduction studies in pregnant rats and rabbits did not show impaired fertility or harm to the fetus. Taliglucerase or velaglucerase administration in pregnant women should only occur if clearly needed.

• Additionally, no human studies have investigated the effects of imiglucerase, taliglucerase in breast-fed infants.

BILLING/CODING INFORMATION:

HCPCS Coding:

J1786

Injection, imiglucerase, 10 units

J3060

Injection, taliglucerase alfa, 10 units

J3385

Injection, velaglucerase alfa, 100 units

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: 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.

Hemoglobin: normal hemoglobin values vary, but in general the following table describes levels for different populations.

Normal Hemoglobin Values (g/dL) Ranges

 

Male

Female

Newborn

14.7 – 18.6

12.7 – 18.3

6 months to 2 years

10.3 – 12.4

10.4 – 12.4

2-6 years

10.5 – 12.7

10.7 – 12.7

6-12 years

11.0 – 13.3

10.9 – 13.3

12-18 years

11.5 – 14.8

11.2 – 13.6

Greater than 18 years

13.5 – 17.5

12 – 16

RELATED GUIDELINES:

Oral Therapy for Gaucher Disease, 09J0000-76

OTHER:

None applicable.

REFERENCES:

  1. Alglucerase. In: McEvoy GK, editor. AHFS drug information 2012 [monograph on the internet]. Bethesda (MD): American Society of health-System Pharmacists; 2012 [cited 2013 Apr 19]. Available from: http://online.statref.com. Subscription required to view
  2. © Copyright 2010, AAPC Code Crosswalk.
  3. American Medical Association CPT Coding, 2011 professional edition.
  4. Barton NW, Brady RO, Dambrosia JM, et al. (1991). Replacement therapy for inherited enzyme deficiency-macrophage targeted glucocerebrosidase for Gaucher disease. New England Journal of Medicine, 324 (21): 1464-1470.
  5. Beutler E, Demina A, et al. (1995). The clinical course of treated and untreated Gaucher Disease. A Study of 45 patients. Blood Cells, Molecules, and Diseases 21 (10): 860108.
  6. Beutler E, Kay A, et al. (1991). Enzyme replacement therapy for Gaucher Disease. Blood 78 (5): 1183-1189.
  7. Beutler E. (1993). Modern diagnosis and treatment of Gaucher Disease. AJDC 147: 1175-1182.
  8. Beutler E. (1994). Economic malpractice in the treatment of Gaucher Disease. The American Journal of Medicine July 1994: 1-2.
  9. Beutler E. (2000). Commentary: Dosage-response in the treatment of Gaucher Disease by enzyme replacement therapy. Blood Cells, Molecules, and Diseases 26 (4): 303-306.
  10. Cerezyme (imiglucerase) [package insert]. Genzyme Corp. Cambridge (MA): December 2012.
  11. Clinical Pharmacology. [database online]. Tampa, FL: Gold Standard, Inc.; 2015. URL: www.clinicalpharmacology-ip.com. Accessed 05/20/2017.
  12. Cox T, Lachmann R, Hollak C, et al. (2000). Novel oral treatment of Gauches disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. The Lancet; 355 (9214): 1481-1485.
  13. ECRI. Enzyme Replacement Therapy (ERT) for Gaucher Disease. Custom Hotline Response: ECRI updated 09/12/05.
  14. Elelyso (taliglucerase alfa) [package insert]. Pfizer Laboratories Inc. New York (NY): May 2012.
  15. Facts & Comparisons E Answers. Accessed 09/13/11.
  16. Figueroa, ML, Rosenbloom, BE, Kay, AC, et al. (1992). A less costly regimen of alglucerase to treat Gaucher’s disease. New England Journal of Medicine, 327 (23): 1632-1636.
  17. Garber AM, Clarke AI, Goldman DP and Gluck ME (1992). Federal and private roles in the development and provision of alglucerase therapy for Gaucher disease. US Government Printing Office, 1992.
  18. Imiglucerase. In: McEvoy GK, editor. AHFS drug information 2012 [monograph on the internet]. Bethesda (MD): American Society of health-System Pharmacists; 2012 [cited 2013 Apr 19]. Available from: http://online.statref.com. Subscription required to view
  19. Ingenix HCPCS Level II, Expert 2011.
  20. Ingenix ICD-9-CM. Codes for Physicians – Volumes 1 & 2, Expert 2011.
  21. International Collaborative Gaucher Group Registry Update, August 1995.
  22. Micromedex Healthcare Series [Internet database]. Greenwood village, Colo: Thomson Healthcare. Updated periodically. Accessed 05/20/2017
  23. Mistry P, Wraight E, Cox T. (1996). Therapeutic deliver of proteins to macrophages: implications for treatment of Gaucher’s disease. The Lancet; 348 (9041): 1555-1559.
  24. Mistry PK, Sadan S, Yang R, Yee J and Yang M. Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among Hematologists-Oncologists and an opportunity for early diagnosis and intervention. Am J Hematol. 2007 May 9.
  25. National Institutes of Health Technology Assessment Conference Statement February 27 – March 1, 1995. Gaucher Disease: Current issues in diagnosis and treatment (1995).
  26. Southern California Kaiser Permanente Drug Formulary Criteria for Ceredase, 2001.
  27. Vpriv (velaglucerase alfa) [package insert]. Shire Human Genetic Therapies, Inc. Cambridge (MA): Apr 2013.
  28. Weinreb N, Barranger J, Packman S, Prakash-Cheng A, Rosenbloom B, Sims K, Angell J, Skrinar A and Pastores G. Imiglucerase (Cerezyme) improves quality of life in patients with skeletal manifestations of Gaucher disease. Clin Genet. 2007 Jun;71(6):576-88.
  29. Zimran A, Elstein D, Levy-Lahad E, et al. (1995). Replacement therapy with imiglucerase for type 1 Gaucher’s disease. The Lancet 345 (8963): 1479-1480.
  30. Zimran A, Hollak CEM, et al. (1993). Home treatment with intravenous enzyme replacement therapy for Gaucher Disease: An international collaborative study of 33 patients. Blood, 82 (4): 1107-1109.

COMMITTEE APPROVAL:

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

GUIDELINE UPDATE INFORMATION:

04/15/02

Original Medical Coverage Guideline Developed.

01/01/06

CPT coding update, deleted expired codes: 90780, 90781, added new codes 90765 and 90766.

08/15/05

Revised and Updated: added Ceredase to the title, added chemical name to the subject, updated dosage/administration, deleted precautions, contraindications, updated when services are not covered, reimbursement information, updated ICD-9 Coding, references, and the related internet links.

09/15/06

Biennial review and updated references.

01/01/07

MCG revised to include Medicare Part D as program exception.

08/15/07

Reviewed guideline: Reformatted guideline, maintain current coverage and limitations, requested MPAF pxdx audit, added paragraph regarding Gaucher disease, updated internet links and updated references.

01/01/09

Annual HCPCS coding update: deleted 90765 and 90766; added 96365 and 96366.

08/15/09

Review and revision to guideline; consisting of changing the name and updating references.

06/15/10

Revision to guideline; consisting of adding new agent.

11/15/10

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

01/01/11

Revision to guideline; consisting of updating coding.

11/15/11

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

07/15/12

Revision to guideline; consisting of adding new product.

11/15/12

Review and revision to guideline; consisting of revising position statement, dosage/administration section, precautions/warnings section; updating references; adding contraindications section

07/15/13

Review and revision to guideline; consisting of revising position statement, updating references and coding.

10/15/13

Revision to guideline; consisting of removing algulcerase (Ceredase) from guideline (product is obsolete).

01/01/14

Revision to guideline; consisting of code update.

05/15/14

Review and revision to guideline; consisting of revising position statement to include continuation criteria.

11/15/14

Revision to guideline; consisting of description, position statement, dosing/administration

07/15/15

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

11/01/15

Revision: ICD-9 Codes deleted.

01/15/16

Revision to guidelines; 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 description and position statement.

Date Printed: October 20, 2017: 11:57 AM