Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Enzyme Replacement for the Treatment of Gaucher's Disease

Policy #:08.00.51i

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

Imiglucerase (Cerezyme®), or velaglucerase alfa (VPRIV®) are considered medically necessary and, therefore, covered, as a long-term enzyme replacement therapy (ERT) for pediatric and adult individuals with a confirmed diagnosis of Type 1 Gaucher's disease or those with clinical non-neuropathic manifestations of Type 3 Gaucher's disease, resulting in one or more of the following conditions:
  • Anemia
  • Bone disease
  • Hepatomegaly or splenomegaly
  • Thrombocytopenia

Taliglucerase alfa (Elelyso®) is considered medically necessary and, therefore, covered, as a long-term ERT for adult individuals with a confirmed diagnosis of Type 1 Gaucher's disease or those with clinical non-neuropathic manifestations of Type 3 Gaucher's disease, resulting in one or more of the following conditions:
  • Anemia
  • Hepatomegaly or splenomegaly
  • Thrombocytopenia

COMPANY-DESIGNATED PREFERRED PRODUCTS
Although there are several brands of enzyme replacement therapy on the market for the treatment of Gaucher disease, there is no reliable evidence of the superiority of any one brand compared to other brands. The Company has designated VPRIV® as its preferred product.

This product is less costly and at least as likely to produce equivalent therapeutic results as the non-preferred products, which include, but are not limited to: Cerezyme® and Elelyso®.

For individuals who meet the above medical necessity criteria, use of the Company-designated preferred product, VPRIV®, is considered medically necessary and, therefore, covered.

NON-PREFERRED PRODUCTS
For individuals who meet the above medical necessity criteria, use of non-preferred products (which include, but are not limited to Cerezyme® and Elelyso®) is considered medically necessary and, therefore, covered in at least one the following instances*:
  • The individual has a documented contraindication, or documented non-response, to the preferred product (VPRIV®).
  • The individual is currently receiving or has previously received a non-preferred product.

*Requests for the use of non-preferred products that do not meet either of these conditions are considered not medically necessary and, therefore, not covered.

NOT MEDICALLY NECESSARY

For individuals receiving enzyme replacement therapy (ERT), use of non-preferred products (which include, but are not limited to Cerezyme® and Elelyso®), is considered not medically necessary and, therefore, not covered unless there is a documented contraindication to the preferred products (e.g., VPRIV®) because more cost-effective alternatives are available.

NOT ELIGIBLE FOR REIMBURSEMENT

Alglucerase (Ceredase®) is no longer manufactured and has been withdrawn from market, therefore, it is not eligible for reimbursement.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for imiglucerase (Cerezyme®), velaglucerase alfa (VPRIV®), or taliglucerase alfa (Elelyso®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, enzyme replacement therapy for the treatment of Gaucher's disease is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

HOME INFUSION

Enzyme replacement therapy for the treatment of Gaucher's disease may be available under the medical benefit for applicable lines of business through home infusion providers. Member’s benefit for home infusion should be verified.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA approved the use of alglucerase (Ceredase®) in April 1991 for long-term ERT for individuals who have a confirmed diagnosis of Type 1 Gaucher's disease.

The FDA approved the use of imiglucerase (Cerezyme®) in May 1994 for long-term ERT for individuals who have a confirmed diagnosis of Type 1 Gaucher's disease.

The FDA approved the use of velaglucerase alfa (VPRIV®) on February 26, 2010 for long-term ERT for individuals who have a confirmed diagnosis of Type 1 Gaucher's disease.

The FDA approved the use of taliglucerase alfa (Elelyso®) on May 1, 2012 for long-term ERT for adults who have a confirmed diagnosis of Type 1 Gaucher's disease.

PEDIATRIC USE

The safety and effectiveness of imiglucerase (Cerezyme®) have not been established individuals younger than 2 years of age.

The safety and effectiveness of velaglucerase alfa (VPRIV®) have not been established individuals younger than 4 years of age.

The safety and effectiveness of taliglucerase alfa (Elelyso®) have not been established individuals younger than 4 years of age.

Description

Gaucher's disease, also called Gaucher disease, is a rare, genetic, metabolic disorder caused by a deficiency of the enzyme glucocerebrosidase. Deficiency of glucocerebrosidase causes an accumulation of glucosylceramide, which is highly insoluble, in storage cells of the liver, spleen, bone marrow, and lymph nodes. Disease variants are classified according to the presence or absence of neurologic involvement and the rate of its progression into three major clinical subtypes: Types 1, 2, and 3. Type 1, the most common, is a chronic, nonneuronopathic, or adult form; it is the most prevalent. Although Type 1 Gaucher's disease is sometimes referred to as the adult form, symptoms of Type 1 can manifest at any age. Symptoms include bruising easily; fatigue due to anemia and low blood platelets; an enlarged liver and spleen; skeletal disorders; and, in rare instances, lung and kidney involvement. In Type 2 Gaucher's disease, liver and spleen enlargement are apparent by 3 months of age. It is an acute, neuronopathic, or infantile form, characterized by rapid neurologic deterioration; survival beyond 2 years of age is rare. Type 3 is a subacute, neuronopathic, or juvenile form, with a variable course marked by slowly progressive neurologic involvement and some characteristics of Type 1 and 2. Liver and spleen enlargement is a variable, along with brain involvement, which becomes apparent when marked by seizures.

In April 1991 the US Food and Drug Administration (FDA) approved alglucerase (Ceredase®), as an orphan drug (a drug used to treat, prevent, or diagnose a rare disease), for use as long-term enzyme replacement therapy (ERT) for children, adolescents, and adult individuals with a confirmed diagnosis of Type 1 Gaucher's disease who have signs and symptoms severe enough that results in one or more of the following conditions:
  • moderate-to-severe anemia
  • thrombocytopenia with bleeding tendency
  • bone disease
  • significant hepatomegaly or splenomegaly

Alglucerase (Ceredase®) is a modified form of the human enzyme, beta-glucocerebrosidase, prepared from a large pool of human placental tissue collected from selected donors. The quantity of the drug is based on the amount that is collected from selected donors. Due to this limit alglucerase (Ceredase®) was phased out and replaced with imiglucerase (Cerezyme®).

In May 1994 the FDA approved imiglucerase (Cerezyme®), as an orphan drug, for the use as a long-term ERT for pediatric and adult individuals with a confirmed diagnosis of Type 1 Gaucher's disease who have signs and symptoms severe enough that results in one or more of the following conditions:
  • anemia
  • thrombocytopenia
  • bone disease
  • hepatomegaly or splenomegaly

Imiglucerase (Cerezyme®) is an analogue of the human enzyme, beta-glucocerebrosidase, produced by recombinant DNA technology. It differs from placental glucocerebrosidase by one amino acid at position 495, where histidine is substituted for arginine. Imiglucerase (Cerezyme®) is equivalent to alglucerase (Ceredase®). In clinical trials, imiglucerase (Cerezyme®) improved anemia and thrombocytopenia, reduced spleen and liver size, and decreased cachexia to a degree similar to that observed with alglucerase
(Ceredase®).

In February 2010 velaglucerase alfa (VPRIV®) was FDA-approved for long-term ERT for pediatric and adult individuals with Type 1 Gaucher's disease. Velaglucerase alfa (VPRIV®) has the same amino acid sequence as the naturally occurring human enzyme, glucocerebrosidase. The safety and effectiveness of velaglucerase alfa (VPRIV®) was assessed in three clinical studies of naïve individuals to ERT and individuals who switched from imiglucerase (Cerezyme®) to velaglucerase alfa (VPRIV®). Per the FDA-approved prescribing information, individuals switching from imiglucerase (Cerezyme®) to velaglucerase alfa (VPRIV®) can begin treatment with velaglucerase alfa (VPRIV®) at the same stable dose of imiglucerase (Cerezyme®).

In May 2012 taliglucerase alfa (Elelyso®) was FDA-approved for long-tern ERT for adult and pediatric individuals with a confirmed diagnosis of Type 1 Gaucher's disease. Taliglucerase alfa (Elelyso®) is a recombinant active form of the lysosomal enzyme, glucocerebrosidase. Taliglucerase alfa (Elelyso®) is the first FDA-approved plant-cell-based ERT for Gaucher disease derived using genetically engineered carrot cells. Safety and efficacy of taliglucerase alfa (Elelyso®) was established in three studies containing individuals naïve to ERT and individuals switching from imiglucerase (Cerezyme®) to taliglucerase alfa (Elelyso®). Most individuals in the studies showed an improvement in their anemia, thrombocytopenia, and/or a decrease in their liver and spleen size.

According to published research, systemic manifestations of Type 3 Gaucher’s disease can be reduced in individuals treated with ERT, but neurologic manifestations of Gaucher's disease is not affected by ERT. There is evidence that replacement of the missing enzyme glucocerebrosidase through ERT may improve the health outcome and quality of life in individuals significantly affected by Type 3 Gaucher’s disease. However, treatment with ERT was ineffective for individuals with Type 2 disease, the neuronopathic form, as it does not alter the neurodegenerative course of the Type 2 disease.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


Altarescu G, Hill S, Wiggs E, et al. The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease. J Pediatr. 2001;138(4):539-547.

American Hospital Formulary Service (AHFS). Drug Information 2016. Imiglucerase. 05/03/2017. [Lexicomp Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 5, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2016. Taliglucerase alfa. 05/03/2017 [Lexicomp Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 5, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2016. Velaglucerase alfa. 05/03/2017 [Lexicomp Web site]. Available at:http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 5, 2017.

Andersson HC, Charrow J, Kaplan P, et al; and the International Collaborative Gaucher Group U.S. Regional Coordinators. Individualization of long-term enzyme replacement therapy for Gaucher disease. Genet Med. 2005:7(2):105-110.

Charrow J, Andersson HC, Kaplan P, et al. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr. 2004;144(1):112-120.

Elsevier’s Gold Standard Clinical Pharmacology Compendium.Alglucerase. 06/18/2015. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed June 6, 2017.

Elsevier’s Gold Standard Clinical Pharmacology Compendium.Imiglucerase. 01/23/2017. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed June 6, 2017.

Elsevier’s Gold Standard Clinical Pharmacology Compendium.Taliglucerase alfa. 08/29/2014. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed June 6, 2017.

Elsevier’s Gold Standard Clinical Pharmacology Compendium. Velaglucerase alfa. 10/26/2016. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed June 6, 2017.

Genzyme Therapeutics. Cerezyme® (imiglucerase for injection). [Genzyme Web site]. Available at: http://www.cerezyme.com/ . Accessed June 2, 2017.

Grabowski GA. Endocrinology and Metabolism. In: Braunwald E, Fauci AS, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill Professional Publishing; 2001: 2276-2281.

Kaplan P. Revised recommendations for the management of Gaucher disease in children. Eur J Pediatric. 2013; 172:447-458.

Lexi-Drugs Compendium. Imiglucerase alfa. Lexicomp Online Web site]. 04/13/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 2, 2017.

Lexi-Drugs Compendium. Taliglucerase alfa. [Lexicomp Online Web site]. 05/22/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 2, 2017.

Lexi-Drugs Compendium. Velaglucerase alfa. [Lexicomp Online Web site]. 05/15/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 2, 2017.

Linari S. Clinical manifestations and management of Gaucher disease. Clin Cases Miner Bone Metab. 2015 May-Aug. 12(2):157-164.

Micromedex® Healthcare Series [Internet database]. Alglucerase. Greenwood Village, CO: Thomson Micromedex. 11/11/2016. Available at: http://www.micromedexsolutions.com [via subscription only]. Accessed June 5, 2017.

Micromedex® Healthcare Series [Internet database]. Imiglucerase. Greenwood Village, CO: Thomson Micromedex. 06/01/2017. Available at: http://www.micromedexsolutions.com [via subscription only]. Accessed June 5, 2017.

Micromedex® Healthcare Series [Internet database]. Taliglucerase alfa. Greenwood Village, CO: Thomson Micromedex. 10/13/2016. Available at: http://www.micromedexsolutions.com [via subscription only]. Accessed June 5, 2017.

Micromedex® Healthcare Series [Internet database]. Velaglucerase alfa. Greenwood Village, CO: Thomson Micromedex. 08/12/2016. Available at: http://www.micromedexsolutions.com [via subscription only]. Accessed June 5, 2017.

National Institute of Neurological Disorders and Stroke (NINDS). NINDS Gaucher’s disease information page. [NINDS Web site]. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Gaucher-Disease-Information-PageAccessed June 6, 2017.

Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol. 2004;41(4 suppl 5):4-14.

Schiffmann R, Heyes MP, Aerts JM, et al. Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease. Ann Neurol. 1997;42:613-621.

US Food and Drug Administration (FDA). Ceredase (Alglucerase). Approval history, letters, reviews, related documents, and label information. [FDA Web site]. 02/09/2006. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed June 6, 2017.

US Food and Drug Administration (FDA). Cerezyme (Imiglucerase). Approval history, letters, reviews, related documents, and label information. [FDA Web site]. 11/13/2002. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails Accessed June 6, 2017.

US Food and Drug Administration (FDA). Taliglucerase Alfa (Elelyso). Approval history, letters, reviews, related documents, and label information. [FDA Web site]. 05/01/12. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed June 6, 2017.

US Food and Drug Administration (FDA). Velagluceraase Alfa (VPRIV). Approval history, letters, reviews, related documents, and label information. [FDA Web site]. 02/26/10. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed June 6, 2017.

Vellodi A, Bembi B, De Villemeur TB, et al. Management of neuronopathic Gaucher disease: a European consensus. J Inherit Metab Dis. 2001;24:319-327.

Vellodi A. Management of neuronopathic Gaucher disease: Revised recommendations. J Inherit Metab Dis. 2009;32:660-664.

Weinreb NJ, Aggio MC, Andersson HC, et al. Gaucher disease type 1: revised recommendations on evaluations and monitoring for adult patients. Semin Hematol.
2004;41(4 suppl 5):15-22.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

E75.22 Gaucher disease


HCPCS Level II Code Number(s)



MEDICALLY NECESSARY

J1786 Injection imiglucerase, 10 units

J3060 Injection, taliglucerace alfa, 10 units

J3385 Injection, velaglucerase alfa, 100 units

S9357 Home infusion therapy, enzyme replacement intravenous therapy; (e.g., Imiglucerase); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem


NOT ELIGIBLE FOR REIMBURSEMENT

THE FOLLOWING CODE REPRESENTS ALGLUCERASE (CEREDASE®), WHICH IS NO LONGER MANUFACTURED AND HAS BEEN WITHDRAWN FROM THE MARKET:

J0205 Injection, alglucerase, per 10 units



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions from 08.00.51i
10/24/2018This policy has been reissued in accordance with the Company's annual review process.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 10/24/2017
Version Issued Date: 10/24/2017
Version Reissued Date: 10/25/2018

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