Medical Policy Bulletin

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Title:

Alglucerase (Ceredase®) and Imiglucerase (Cerezyme®)

Policy #:

08.00.51b

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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. 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.

Intent

The intent of this policy is to communicate the medical necessity criteria for alglucerase (Ceredase®) and imiglucerase (Cerezyme®). For information on policies related to this topic, refer to the Cross References Table in this policy.

Description:

Gaucher's 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: Type 1, 2, and 3. Type 1 is a chronic, nonneuronopathic, or adult form; it is the most prevalent. Although Type 1 Gaucher disease is sometimes referred to as the adult form, symptoms of Type 1 can manifest at any age. Type 2 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. The US Food and Drug Administration (FDA) approved alglucerase (Ceredase®) and imiglucerase (Cerezyme®) as long-term enzyme replacement therapy in children and adults who have a confirmed diagnosis of Type 1 Gaucher's disease that results in one or more of the following: Anemia Thrombocytopenia Bone disease Hepatomegaly or splenomegaly Alglucerase (Ceredase®) is a modified form of the human enzyme, beta-glucocerebrosidase; it is prepared from a large pool of human placental tissue collected from selected donors. 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. The FDA approved both alglucerase (Ceredase®) and imiglucerase (Cerezyme®) as orphan drugs (a drug used to treat, prevent, or diagnose a rare disease). 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®). According to Schiffmann, et al. and Altarescu, et al., systemic manifestation of Type 3 Gaucher’s disease reversed in almost all individuals treated with enzyme replacement therapy, but neurologic damage remained stable. There is evidence that replacement of the missing enzyme glucocerebrosidase through enzyme replacement therapy may improve the health outcome and quality of life in individuals significantly affected by Type 3 Gaucher’s disease. Enzyme replacement therapy was found effective in reducing disease symptoms and reversing the course of the disease for individuals with Type 1 and most individuals with Type 3 Gaucher disease. However, treatment with enzyme replacement was ineffective for individuals with Type 2 disease, the neuronopathic form, as it does not alter the neurodegenerative course of the Type 2 disease.

Policy

Alglucerase (Ceredase®) or imiglucerase (Cerezyme®) is considered medically necessary and, therefore, covered as a long-term enzyme replacement therapy for adults who have a confirmed diagnosis of Type 1 or Type 3 Gaucher's disease that is symptomatic, resulting in one or more of the following conditions: Anemia Bone disease Hepatomegaly or splenomegaly Thrombocytopenia Alglucerase (Ceredase®) or imiglucerase (Cerezyme®) is considered medically necessary and, therefore, covered as a long-term enzyme replacement therapy for children (less than 18 years of age) with a confirmed diagnosis of Type 1 or Type 3 Gaucher's disease manifesting physical signs or symptoms, resulting in any of the following conditions: Anemia Bone disease Delay in growth and development Hepatomegaly or splenomegaly Thrombocytopenia Symptomatic disease (such as, but not limited to: abdominal or bone pain, fatigue, exertional limitations, weakness, cachexia) All other uses of alglucerase (Ceredase®) and imiglucerase (Cerezyme®) (eg, use in Type 2 Gaucher's disease, use in asymptomatic Gaucher's disease, use in combination with miglustat [Zavesca®]) are considered experimental/investigational and, therefore, not covered because their safety and/or efficacy cannot be established by review of the available published literature. PRECERTIFICATION OR PREAPPROVAL REQUIREMENTS For most of the Company's products, alglucerase (Ceredase®) or imiglucerase (Cerezyme®) requires precertification or preapproval, regardless of place of service. Individual product requirements must be verified.

Guidelines

Alglucerase (Ceredase®) and imiglucerase (Cerezyme®) are administered by intravenous infusion over one to two hours. BENEFIT APPLICATION Subject to the terms and conditions of the applicable benefit contract, alglucerase (Ceredase®) and imiglucerase (Cerezyme®) may be covered under the medical benefit of the Company’s products when medical necessity criteria in the medical policy are met. A medication or class of medications may be a product or group contract exclusion. Individual benefits must be verified. HOME INFUSION Alglucerase (Ceredase®) and imiglucerase (Cerezyme®) are available under the medical benefit for applicable lines of business through infusion providers. For more information, refer to the policy addressing infusion therapy services. MEDICARE This policy is consistent with Medicare's coverage determination. For Medicare Advantage members, alglucerase (Ceredase®) or imiglucerase (Cerezyme®) is available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. US FOOD AND DRUG ADMINISTRATION (FDA) STATUS The FDA approved the use of alglucerase (Ceredase®) in April 1991 for long-term enzyme replacement therapy for individuals who have a confirmed diagnosis of Type 1 Gaucher's disease. Imiglucerase (Cerezyme®) received FDA approval in May 1994 for long-term enzyme replacement therapy for individuals who have a confirmed diagnosis of Type 1 Gaucher's disease.

References

Alglucerase. In: DrugPoints. Greenwood Village, CO: Thomson Micromedex; 2007. Available at: http://www.thomsonhc.com [via subscription only]. Accessed November 21, 2008. 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 2008. Alglucerase. [STAT!Ref Web site]. Available at: http://online.statref.com [via subscription only]. Accessed November 21, 2008. American Hospital Formulary Service (AHFS). Drug Information 2008. Imiglucerase. [STAT!Ref Web site]. Available at: http://online.statref.com [via subscription only]. Accessed November 21, 2008. 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. Deegan P, Hughes D, Mehta A, et al. UK national guideline for adult Gaucher disease. [UK Department of Health Web site]. 08/01/05. Available at: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4118405. Accessed November 21, 2008. Genzyme Therapeutics. Cerezyme® (imiglucerase for injection). [Genzyme Web site]. Available at: http://www.cerezyme.com/home/default.asp. Accessed October 13, 2008. Genzyme Therapeutics. Disease Management of Type 1 Gaucher Disease. [Genzyme Web site]. Available at: http://www.cerezyme.com/healthcare/goals/cz_TCTreatmentGuide.pdf. Accessed October 13, 2008. 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. Highmark Medicare Services. Local Coverage Determination (LCD). I-6J: Approved drugs and biologicals. [Highmark Medicare Services Web site]. Original: 03/29/93. (Revised: 08/20/08). Available at: http://www.highmarkmedicareservices.com/policy/partb/i1/i6h.html. Accessed October 13, 2008. Imiglucerase. In: DrugPoints. Greenwood Village, CO: Thomson Micromedex; 2007. Available at: http://www.thomsonhc.com [via subscription only]. Accessed November 21, 2008. Micromedex® Healthcare Series [Internet database]. Alglucerase. Greenwood Village, CO: Thomson Micromedex. Available at: http://www.thomsonhc.com [via subscription only]. Accessed November 21, 2008. Micromedex® Healthcare Series [Internet database]. Imiglucerase. Greenwood Village, CO: Thomson Micromedex. Available at: http://www.thomsonhc.com [via subscription only]. Accessed November 21, 2008. National Government Services, Inc. Article for beta glucocerebrosidase (Ceredase®/Cerezyme®) - Related to LCD 25820 (A46107). [National Government Services, Inc. Web site]. Original: 12/01/07. (Revised 07/18/08). Available at: http://www.ngsmedicare.com/NGSMedicare/lcd/L25820_att_beta.htm. Accessed November 21, 2008 National Government Services, Inc. Local Coverage Determination (LCD). L25820: Drugs and biologicals, coverage of, for label and off-label uses. [National Government Services, Inc. Web site]. Original: 12/01/07. (Revised: 07/18/08). Available at: http://www.ngsmedicare.com/NGSMedicare/lcd/L25820_active_lcd.htm. Accessed November 21, 2008. National Institute of Neurological Disorders and Stroke (NINDS). NINDS Gaucher’s disease information page. [NINDS Web site]. 02/07/08. Available at: http://www.ninds.nih.gov/disorders/gauchers/gauchers.htm. Accessed November 21, 2008. Pastores GM. Gaucher disease. [GeneTests Web site]. Original: 07/27/00. (Revised March 13, 2008). Available at: http://www.genetests.org/servlet/access?db=geneclinics&site=gt&id=8888892&key=sEoTdys3DWKHh&gry=&fcn=y&fw=wHAd&filename=/profiles/gaucher/index.html. Accessed November 21, 2008. 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]. 04/05/91. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed November 21, 2008. US Food and Drug Administration (FDA). Cerezyme (Imiglucerase). Approval history, letters, reviews, related documents, and label information. [FDA Web site]. 05/23/94. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed November 21, 2008. 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. 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 Table

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.

Code System	Code Number(s) and Narrative(s)
CPT	N/A
ICD Procedure	N/A
ICD Diagnosis	272.7: Lipidoses
HCPCS Level II	J0205: Injection, alglucerase, per 10 units J1785: Injection, imiglucerase, per unit S9357: Home infusion therapy, enzyme replacement intravenous therapy; (eg, imiglucerase); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
Revenue Codes	N/A

Cross References

Version Effective Date: 10/09/2007