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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:006
Effective Date: 09/11/2020
Original Policy Date:01/01/1992
Last Review Date:08/11/2020
Date Published to Web: 10/10/2018
Subject:
Gaucher Disease Therapy

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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In Gaucher disease, the enzyme glucocerebrosidase is either absent or has greatly diminished activity. Gaucher disease is often suspected in individuals with characteristic bone involvement, visceral and hematologic changes, but clinical findings alone are not diagnostic. Gaucher disease encompasses a broad range of clinical symptoms from a perinatal-lethal form to an asymptomatic form. The most efficient method of establishing the diagnosis of Gaucher disease is the assay of glucocerebroside activity in the peripheral blood samples. The identification of three clinical subtypes is also useful in determining the disease management. Type 1 Gaucher is the most prominent of the 3 types (it is seen in approximately 99% of cases). It is characterized by the presence of bone disease, hepatosplenomegaly, anemia and thrombocytopenia with the absence of neurologic symptoms. Types 2 and 3 are characterized by the presence of primary neurologic disease along with the Type 1 symptoms. The age of onset and the rate of disease progression are the differentiating factors between Type 2 and Type 3 Gaucher.

Currently, enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) are the two different types of treatment options for Gaucher disease. Four medications are available for ERT, alglucerase (Ceredase), imiglucerase (Cerezyme), velaglucerase alfa (Vpriv), and taliglucerase alfa (Elelyso). Alglucerase is a modified form of the human enzyme B-glucocerebrosidase and is prepared from human placental glucocerebrosidase. Imiglucerase is an analogue of B-glucocerebrosidase produced by recombinant DNA technology. Velaglucerase alfa is a hydrolytic lysosomal enzyme, and taliglucerase alfa, a hydrolytic lyosomal glucocerebroside-specific enzyme. Literature indicates that ERT does not cross the blood brain barrier and thus, is not a sufficient treatment for the neuronopathic manifestations seen in patients with Type 2 and Type 3 Gaucher disease. Alglucerase, imiglucerase and velaglucerase alfa are FDA approved for the treatment of Type 1 Gaucher disease in the adult and pediatric population, and taliglucerase alfa is FDA approved for the treatment of Type 1 Gaucher disease in adult population only.

There are two SRT available on the market. Miglustat (Zavesca) is an oral preparation of SRT and has an FDA approved indication for mild to moderate Type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option. Miglustat is a competitive and reversible inhibitor of the enzyme glucosylceramide synthetase, the initial enzyme in a series of reactions resulting in the synthesis of most glycospingolipids. Eliglustat (Cerdelga) also inhibits glucosylceramide synthase. It is FDA approved for long-term treatment of adult patients with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs) or poor metabolizers (PMs) as detected by an FDA-approved test. It was studied in a head-to-head trial against imiglucerase in treatment experienced patients and was found to be non-inferior to imiglucerase.


Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

The requirements of the Horizon BCBSNJ Gaucher Disease Therapy Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

1. Please refer to a separate policy on Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) under the Drug Section.

2. Alglucerase (Ceredase), imiglucerase (Cerezyme), miglustat (Zavesca), velaglucerase alfa (Vpriv), taliglucerase alfa (Elelyso), or eliglustat (Cerdelga) must be prescribed by the treating physician that is a specialist in the area of the patient's diagnosis (e.g. hematologist, geneticist).

3. Alglucerase, imiglucerase, velaglucerase alfa, taliglucerase alfa or eliglustat is considered medically necessary based on the FDA approved indication for use as long-term therapy for members (2 years of age and older for alglucerase or imiglucerase, 4 years of age and older for velaglucerase alfa & taliglucerase alfa,18 years and older for eliglustat) if the following criteria are met:

    • Confirmed diagnosis of Type I Gaucher disease by either of the following (documentation of medical records required):
      • Deficiency of glucosyleramidase (also known as acid B-glucosidase or glucocerebrosidase) in peripheral blood leukocytes or other nucleated cells; OR
      • Confirmation of biallelic pathogenic variants in the GBA gene; AND
    • Must be used as a single agent; AND
    • Disease results in one or more of the following conditions (applicable to adults only) (documentation of medical records required):
      A. Anemia (hemoglobin less than or equal to 11g/dL (women) or 12g/dL (men)
      B. Thrombocytopenia (platelet count less than or equal to 120,000/mm3
      C. Skeletal disease - (e.g. lesions, remodeling defects and/or deformity of long bones, osteopenia/osteoporosis, etc.)
      D. Moderate to severe hepatomegaly (liver size 1.25 or more times normal volume ) or splenomegaly (spleen size 5 or more times normal volume)
      E. Symptomatic disease, including bone pain, fatigue, dyspnea, angina, abdominal distension, diminished quality of life, etc.
4. For initial requests for newly diagnosed patients, eliglustat is considered medically necessary as first-line treatment if:
    • Patient is at least 18 years of age AND
    • Patient has completed an FDA-cleared test to determine CYP2D6 genotype and is confirmed not to be an Ultra-rapid metabolizer AND
    • Patient does not have pre-existing cardiac disease, long QT syndrome, and concomitant use of Class IA and Class III antiarrhythmics, AND
    • Patient does not have hepatic impairment or moderate to severe renal impairment.
5. For initial requests for newly diagnosed patients, imiglucerase is considered medically necessary as first-line treatment if:
    • Patient is at least 2 years old OR
    • Patient is determined to be a CYP2D6 Ultra-rapid metabolizer OR
    • Patient has tried and failed eliglustat OR
    • Patient has any other contraindication to eliglustat.

6. For initial requests for newly diagnosed patients, alglucerase, velaglucerase alfa, or taliglucerase alfa are considered medically necessary as first-line treatment if:
    • Patient has tried and failed both eliglustat AND imiglucerase, OR
    • Patient has a contraindication to both eliglustat AND imiglucerase.

    [INFORMATIONAL NOTE: Ceredase is no longer actively marketed by the manufacturer. However, it is still distributed worldwide under “compassionate use” registrations for a very small number of patients who exhibit hypersensitivity to Cerezyme (imiglucerase). According to the manufacturer, approximately 5 patients remained on Ceredase therapy as of August 2004 because of Cerezyme hypersensitivity.

    One of the most common side effects of imiglucerase therapy is the development of IgG antibodies, as manifested in 15% of treated patients during the first year of therapy. These patients have a higher risk of hypersensitivity (infusion-associated) reactions. Pre-treatment with antihistamines and/or corticosteroids and reduced rate of infusion have allowed for continued use of Cerezyme in most patients.]

    The most common adverse reactions (≥ 10%) reported with velaglucerase alfa were hypersensitivity reactions. Infusion-related reactions were mild and in treatment-naïve patients, onset occurred mostly during the first 6 months of treatment and occurred less frequently with time.

7. Miglustat (Zavesca) is medically necessary based on the FDA approved indication for the treatment of adults with mild to moderate Type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option due to ineffectiveness, hypersensitivity, allergy, or poor venous access. Miglustat has not been studied and is therefore not recommended in children <18 and >65 years of age.

8. When alglucerase, imiglucerase, miglustat, velaglucerase alfa, taliglucerase alfa, or eliglustat is considered medically necessary, therapy will be approved for 6 months based on the FDA recommended dosing:
    • Alglucerase
        o 2.5 units/kg 3 times a week up to 60 units/kg administered as every 1-4 weeks
          [INFORMATIONAL NOTE: As per the FDA labeled package insert dosing and administration section, Ceredase® (alglucerase injection) is administered by intravenous infusion over 1-2 hours. Dosage should be individualized for each patient. Initial dosage may be as little as 2.5 units/kg of body weight 3 times a week up to as much as 60 units/kg administered as frequently as once a week or as infrequently as every 4 weeks. 60 units/kg every 2 weeks is the dose for which the most data are available. Disease severity may dictate that drug be initiated with relatively high doses or relatively frequent administration. After patient response is well-established, a reduction in dosage may be attempted for maintenance therapy. Progressive reductions can be made at intervals of 3-6 months while carefully monitoring response parameters.]
    • Imiglucerase
        o 2.5 units/kg 3 times a week up to 60 units/kg once every 2 weeks
          [INFORMATIONAL NOTE: As per the FDA labeled package insert, Cerezyme® (imiglucerase for injection) is administered by intravenous infusion over 1-2 hours. Dosage should be individualized to each patient. Initial dosages range from 2.5 U/kg of body weight 3 times a week to 60 U/kg once every 2 weeks. 60 U/kg every 2 weeks is the dosage for which the most data are available. Disease severity may dictate that treatment be initiated at a relatively high dose or relatively frequent administration. Dosage adjustments should be made on an individual basis and may increase or decrease, based on achievement of therapeutic goals as assessed by routine comprehensive evaluations of the patient’s clinical manifestations.]
    • Miglustat
        o 100 mg three times daily; dose reduction to 100mg once or twice daily may be permitted in patients due to adverse effects (e.g.: diarrhea or tremor)
Renal Impairment
Adjusted Creatinine Clearance (in ml/min/1.73m3)
Recommendations
Mild
50-70
Start dose at 100 mg twice a day
Moderate
30-50
Start dose at 100 mg once a day
Severe
<30
Use is not recommended
      • Velaglucerase alfa
          o 60 units/kg administered every other week; dosage can be adjusted based on achievement and maintenance of each patient’s therapeutic goals
      • Taliglucerase alfa
          o 60 units/kg administered every other week; dosage can be adjusted based on achievement and maintenance of each patient’s therapeutic goals
          o Patients previously stabilized on imiglucerage are recommended to begin taliglucerase alfa at that same dose when they switch
            [INFORMATIONAL NOTE: As per the FDA labeled package insert, dosing and administration section:
            • Treatment-naïve patients: The recommended dosage of ELELYSO for long-term treatment is 60 units/kg of body weight administered every other week as a 60 to 120 minute intravenous infusion.
            • Patients switching from imiglucerase: Patients currently being treated with imiglucerase for Type 1 Gaucher disease can be switched to ELELYSO. Patients previously treated on a stable dosage of imiglucerase are recommended to begin treatment with ELELYSO at that same units/kg dosage when they switch from imiglucerase to ELELYSO. Administer ELELYSO for long-term treatment every other week as a 60 to 120 minute intravenous infusion. Dosage adjustments can be made based on achievement and maintenance of each patient's therapeutic goals.]
      • Eliglustat
          o The recommended dosage in adults is based on the patient's CYP2D6 metabolizer status
            • EMs (extensive metabolizers), IMs (intermediate metabolizers): 84 mg twice daily
            • PMs (poor metabolizers): 8 mg once daily
          Poor MetabolizerIntermediate MetabolizerExtensive MetabolizerUltra-rapid metabolizerIndeterminate Metabolizer
          Strong CYP 2D6 inhibitor*Not recommendedNot recommended84 mg orally once dailyNot recommendedNot recommended
          Strong CYP 3A inhibitor**ContraindicatedContraindicated84 mg orally once dailyNot recommendedNot recommended
          Moderate CYP 2D6 inhibitor***Not studied84 mg orally once daily84 mg orally once dailyNot recommendedNot recommended
          Moderate CYP 3A inhibitor****Not recommendedNot recommended84 mg orally once dailyNot recommendedNot recommended
          Weak CYP 2D6 inhibitor*****Not studiedNot studiedNot studiedNot recommendedNot recommended
          Weak CYP 3A inhibitor******Not recommendedNot studiedNot studiedNot recommendedNot recommended
          Strong or Moderate CYP 3A & 2D6 inhibitor*******ContraindicatedContraindicatedContraindicatedNot recommendedNot recommended
          Strong CYP 3A Inducers********Not recommendedNot recommendedNot recommendedNot studiedNot studied
          No Drug interactions84 mg orally once daily84 mg orally twice daily84 mg orally twice dailyNot recommendedNot recommended
        * Strong CYP 2D6 inhibitors: paroxetine, quinidine, fluoxetine, bupropion
        *** Moderate CYP 2D6 inhibitors: terbinafine, duloxetine, cinacalcet
        ****** Weak CYP2D6: Amiodarone, celecoxib, cimetidine, desvenlafaxine, diltiazem, diphenhydramine, Echinacea, escitalopram, febuxostat, gefitinib, hydralazine, hydroxychloroquine, imatinib, methadone,
        oral contraceptives, propafenone, ranitidine, ritonavir, sertraline, telithromycin, verapamil
        ** Strong CYP 3A inhibitors: boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole
        **** Moderate CYP 3A inhibitors: Amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil
        ******* Weak CYP 3A inhibitors: Alprazolam, amiodarone, amlodipine, atorvastatin, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginkgo, goldenseal, isoniazid, nilotinib, oral contraceptives, ranitidine, ranolazine, tipranavir/ritonavir, zileuton
        ******** Strong CYP 3A inducers: rifampin, carbamazepine, phenobarbital, phenytoin, and St. John’s Wort
        *******Strong or moderate CYP 2D6 inhibitors: paroxetine, quinidine, fluoxetine, bupropion, terbinafine, duloxetine, or cinacalcet, AND strong or moderate CYP 3A inhibitors: boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole, amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, or verapamil

    9. Continuation of therapy will be evaluated on an annual basis if patient:
        • Disease response as indicated by one or more of the following (compared to pre-treatment baseline):
          • Improvement in symptoms (e.g. bone pain, fatigue, dyspnea, angina, abdominal distension, diminished quality of life, etc.)
          • Reduction in size of liver or spleen
          • Improvement in hemoglobin/anemia
          • Improvement in skeletal disease
          • Improvement in platelet counts; AND
        • Show no signs of toxicity (e.g. hypersensitivity reactions, etc.)
    10. Combination use of alglucerase, imiglucerase, velaglucerase alfa, taliglucerase alfa, miglustat, or eliglustat with each other is considered investigational.

    [INFORMATIONAL NOTE: Combination therapy with oral miglustat and enzyme replacement has been studied. In a small active-controlled study, miglustat appeared to increase the clearance of imiglucerase (Cerezyme) by 70%; therefore, combination therapy with imiglucerase is not indicated. According to the FDA, there is insufficient data to support the use of miglustat as an add-on therapy for ERT, either to enhance control of the disease or to spare ERT dose. The recommended dose of miglustat for the treatment of adult patients with Type 1 Gaucher disease with no renal impairment is one 100 mg capsule administered orally three times a day at regular intervals. The recommended dose adjustment of miglustat for the treatment of adult patients with Type 1 Gaucher disease with mild renal impairment (adjusted creatinine clearance of 50-70 ml/min/1.73m2 ) is one 100 mg capsule administered orally two times a day at regular intervals. The recommended dose adjustment of miglustat for the treatment of adult patients with Type 1 Gaucher disease with moderate renal impairment (adjusted creatinine clearance of 30-50 ml/min/1.73m2 ) is one 100 mg capsule administered orally one time a day at regular intervals. Use of imiglustat in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73 m2) is not recommended. Miglustat may cause fetal harm and is classified as pregnancy category X. In addition, miglustat may also adversely affect spermatogenesis and sperm parameters. Diarrhea and weight loss were common in clinical trials of patients treated with miglustat, approximately 85% and up to 65% of treated patients, respectively. As per the FDA approved package insert, patients may be instructed to use anti-diarrheal medications or to avoid high-carbohydrate-content foods during treatment if they present with diarrhea. For some patients, it may be necessary to reduce the dose to one 100 mg capsule once or twice daily, gradually increasing the dosage by 100 mg every month. However, diarrhea usually decreases with continued use of miglustat. Cases of peripheral neuropathy and tremor have also been reported in patients. In those who develop parasthesias, burning sensations, or tremor, cessation of treatment may be considered. In clinical trials, these reactions were usually reversible after dosage adjustment or treatment discontinuation.]

    11. Alglucerase, imiglucerase, velaglucerase alfa, taliglucerase alfa, miglustate, or eliglustat is considered investigational in the treatment of type 2 and type 3 Gaucher disease.

    [INFORMATIONAL NOTE: Enzyme replacement therapy is based on provision of sufficient glucosylceramidase enzyme to overcome the block in the catabolic pathway and effect the clearance of the stored substrate. Patients with Type 2 Gaucher disease are not likely to respond to ERT, perhaps because the underlying neuropathology is cell death rather than lysosomal storage of glucosphingolipids. Patients with Type 3 Gaucher disease appear to derive some benefit from ERT, in terms of improvement in visceral manifestations, although long term prognosis remains to be defined for this group of patients. The development of progressive myoclonic seizures in Type 3 Gaucher patients while on ERT appears to indicate a poor prognosis.]

    12. When alglucerase, imiglucerase, velaglucerase alfa or taliglucerase alfa is considered medically necessary, supplies and materials for intravenous administration are also eligible for reimbursement.


    Medicare Coverage:
    There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for these drugs. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy. However, per CMS, HCPCS code J8499 is a noncovered code and therefore, will be denied.

    **Note: Bullet 1 of the policy section referring to Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) does not apply for Medicare Advantage Products.

    Medicaid Coverage:
    For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf


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    Horizon BCBSNJ Medical Policy Development Process:

    This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

    ___________________________________________________________________________________________________________________________

    Index:
    Gaucher Disease Therapy
    Enzyme Replacement Therapy, Gaucher Disease
    Replacement Therapy, Gaucher Disease
    Substrate Replacement Therapy, Gaucher Disease
    Alglucerase (Ceredase)
    Ceredase (Alglucerase)
    Imiglucerase (Cerezyme)
    Cerezyme (Imiglucerase)
    Miglustat (Zavesca)
    Zavesca (Miglustat)
    Velaglucerase alfa (Vpriv)
    Vpriv (Velaglucerase alfa)
    Taliglucerase alfa (Elelyso)
    Elelyso (Taliglucerase alfa)
    Eliglustat (Cerdelga)
    Cerdelga (Eliglustat)

    References:
    1. 2005 Physicians' Desk Reference. 59th Edition. Medical Economics Publishing Company.

    2. ECRI. Target Report #778: Enzyme Replacement Therapy (ERT) for Gaucher's Disease. 06/29/2000.

    3. Cerezyme: a Gaucher disease treatment. [website]. Cambridge (MA): Genzyme Therapeutics; [cited 2000 Feb 24]. <www.genzyme.com/cerezyme>

    4. International Collaborative Gaucher Group (ICGG) Gaucher Registry. [website]. Cambridge (MA): International Collaborative Gaucher Group (ICGG) ; [cited 2000 Feb 24]. <www.gaucherregistry.com/>

    5. Damiano AM, Pastores GM, Ware JE Jr. The health-related quality of life of adults with Gaucher's disease receiving enzyme replacement therapy: results from a retrospective study. Qual Life Res 1998 Jul;7(5):373-86.

    6. Elstein D, Abrahamov A, Hadas-Halpern I, Meyer A, Zimran A. Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease. QJM 1998 Jul;91(7):483-8.

    7. Elstein D, Abrahamov A, Zimran A. Ethical considerations for enzyme replacement therapy in neuronopathic Gaucher disease. Clin Genet 1998 Sep;54(3):179-84.

    8. Erikson A, Astrom M, Mansson JE. Enzyme infusion therapy of the Norrbottnian (type 3) Gaucher disease. Neuropediatrics 1995 Aug;26(4):203-7.

    9. Erikson A, Johansson K, Mansson JE, Svennerholm L. Enzyme replacement therapy of infantile Gaucher disease. Neuropediatrics 1993 Aug;24(4):237-8.

    10. Grabowski GA, Barton NW, Pastores G, Dambrosia JM, Banerjee TK, McKee MA, Parker C, Schiffmann R, Hill SC, Brady RO. Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 1995 Jan 1;122(1):33-9.

      11. Masek BJ, Sims KB, Bove CM, Korson MS, Short P, Norman DK. Quality of life assessment in adults with type 1 Gaucher disease. Qual Life Res 1999 May;8(3):263-8.

      12. Morales LE. Gaucher's disease: a review. Ann Pharmacother 1996 Apr;30(4):381-8.

      13. Pastores GM, Sibille AR, Grabowski GA. Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse effects in 33 patients treated for 6 to 24 months. Blood 1993 Jul 15;82(2):408-16.

      14. Prows CA, Sanchez N, Daugherty C, Grabowski GA. Gaucher disease: enzyme therapy in the acute neuronopathic variant. Am J Med Genet 1997 Jul 11;71(1):16-21.

      15. Rice EO, Mifflin TE, Sakallah S, Lee RE, Sansieri CA, Barranger JA. Gaucher disease: studies of phenotype, molecular diagnosis and treatment. Clin Genet 1996 Mar;49(3):111-8.

      16. Rosenthal DI, Doppelt SH, Mankin HJ, Dambrosia JM, Xavier RJ, McKusick KA, Rosen BR, Baker J, Niklason LT, Hill SC, Miller SP, Brady RO, Barton NW. Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics 1995 Oct;96(4 Pt 1):629-37.

      17. Schiffmann R, Heyes MP, Aerts JM, Dambrosia JM, Patterson MC, DeGraba T, Parker CC, Zirzow GC, Oliver K, Tedeschi G, Brady RO, Barton NW. Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease. Ann Neurol 1997 Oct;42(4):613-21.

      18. Tylki-Szymanska A, Czartoryska B. Enzyme replacement therapy in type III Gaucher disease. J Inherit Metab Dis 1999 Apr;22(2):203-4.

      19. Zimran A, Elstein D, Kannai R, Zevin S, Hadas-Halpern I, Levy-Lahad E, Cohen Y, Horowitz M, Abrahamov A. Low-dose enzyme replacement therapy for Gaucher's disease: effects of age, sex, genotype, and clinical features on response to treatment . Am J Med 1994 Jul;97(1):3-13.

      20. Zimran A, Hollak CE, Abrahamov A, van Oers MH, Kelly M, Beutler E. Home treatment with intravenous enzyme replacement therapy for Gaucher disease: an international collaborative study of 33 patients. Blood 1993 Aug 15;82(4):1107-9.

      21. Charrow J, Esplin JA, Gribble TJ, Kaplan P, Kolodny EH, Pastores GM, Scott CR, Wappner RS, Weinreb NJ, Wisch JS. Gaucher disease: recommendations on diagnosis, evaluation, and monitoring . Arch Intern Med 1998 Sep 14;158(16):1754-60.

      22. Cox T, Lachmann R, Hollak C, et al. Novel oral treatment of Gaucher’s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 2000 Apr;355(9214):1481-5.

      23. Cox TM, Aerts JM, Andria G, et al. The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type 1 (non-neuronopathic) Gaucher disease: a position statement. J Inherit Metab Dis 2003;26(6):513-26.

      24. Heitner R, Elstein D, Aerts J, et al. Low-dose N-butyldeoxynojirimycin (OGT 918) for Type 1 Gaucher Disease. Blood Cells. Molecules, and Diseases 2002;28(2):127-133.

      25. Clinical Trials.gov. Gaucher Disease. Available at [http://clinicaltrials.gov]. Accessed on January 2020.

      26. Takahashi T, Yoshida Y, Sato W, et al. Enzyme therapy in Gaucher disease type 2: an autopsy case. Tohoku J Exp Med 1998;186:143-9.

      27. Frei KP, Schiffmann R. Myoclonus in Gaucher disease. Adv Neurol 2002;89:41-8.

      28. Campbell PE, Harris CM, et al. A model of neuronopathic Gaucher disease. Journal of Inherited Metabolic Disease 2003;26(7):629-39.

      29. 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;144:112-120.

      30. Ceredase® package insert. Genzyme Corporation. Cambridge, MA; November 2006.

      31. Cerezyme® package insert. Genzyme Corporation. Cambridge, MA; April 2018.

      32. Zavesca® (miglustat) package insert. Actelion Pharmaceuticals US, Inc. South San Francisco, CA. November 2017.

      33. Weinreb NJ, Barranger JA, Charrow J, et al. Guidance on the use of miglustat for treating patients with Type 1 Gaucher Disease. American Journal of Hematology. 2005; 80:223-229.

      34. Guggenbuhl P, Grosbois, B, et al. Gaucher disease. Joint Bone Spine. March 2008. 116-124.

      35. Futerman, AH, Jmoudiak M. Gaucher disease: pathological mechanisms and modern management. British Journal of Hematology. 2005. 178-188.

      36. Sidransky, E. Gaucher disease overview. April 23, 2007. http://www.emedicine.com/ped/topic837.htm (accessed 2/24/15).

      37. Kishnani PS, DiRocco M, Kaplan P, et al. A randomized trial comparing the efficacy and safety of imiglucerase (Cerezyme) infusions every 4 weeks versus every 2 weeks in the maintenance therapy of adult patients with Gaucher disease type 1. Mol Genet Metab. 2009 Apr;96(4):164-70. Epub 2009 Feb 4.

      38. Schiffmann R, Fitzgibbon EJ, Harris C, et al. Randomized, controlled trial of miglustat in Gaucher's disease type 3. Ann Neurol. 2008 Nov;64(5):514-22.

      39. Andersson H, Kaplan P, Kacena K, et al. Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics. 2008 Dec;122(6):1182-90.

      40. Weinreb N, Taylor J, Cox T, et al. A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase. Am J Hematol. 2008 Dec;83(12):890-5.

      41. National Gaucher Foundation. [website] Available at: http://www.gaucherdisease.org/. Accessed: February 24, 2015.

      42. August 10, 2009 Press Release. Genzyme Provides Update on Cerezyme Supply and 2009 Financial Information. Available at: http://supplyupdate.genzyme.com/.

      43. Revised Guidance to the U.S. Gaucher Community: Management of Cerezyme® (imiglucerase for injection) Supply. Prepared by the U.S. Cerezyme Stakeholders Working Group (meeting held August 10, 2009). Available at: http://www.gaucherdisease.org/Revised_Guidance_to_the_Gaucher_Community_-_Cerezyme_Stakeholders_Working_Group__%28final_-_17_August_2009%29.pdf.

      44. Vpriv package insert. Shire Human Genetic Therapies, Inc. Cambridge, MA. November 2019.

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      51. Elelyso Prescribing Information. Pfizer. New York, NY. October 2019.

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      Codes:
      (The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

      CPT*

        HCPCS
          J0205
          J1786
          J3385
          J3060
        * CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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