Lysosomal Storage Disorders

POLICY NUMBER

L.5.01.526

Aldurazyme (laronidase)

Cerdelga (eliglustat)

Cerezyme (imiglucerase)

Elaprase (idursulfase)

Elelyso (taliglucerase)

Elfabrio (pegunigalsidase alfa)

Fabrazyme (agalsidase)

Kanuma (sebelipase alfa)

Lumizyme (alglucosidase)

Naglazyme (galsulfase)

Nexviazyme (avalglucosidase alfa-ngpt)

Opfolda (miglustat)

Pombiliti (cipaglucosidase alfa-atga)

Vpriv (velaglucerase)

Zavesca (miglustat)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Lysosomal Storage Disorders (LSDs) are a group of inherited metabolic disorders in which harmful amounts of fatty materials accumulate in various cells and tissues in the body. People with these disorders either do not produce enough of one of the enzymes needed to metabolize or they produce enzymes that do not work properly. Although there is no cure, enzyme replacement therapy is available for some of the LSDs.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy for purposes of Medical Policy review.

Gaucher Disease Type 1

Initial Request: Cerezyme (imiglucerase), Elelyso (taliglucerase) and Vpriv (velaglucerase)The requested medication may be considered medically necessary when ALL of the following criteria are met:

1. The individual has a diagnosis of Gaucher disease Type 1;

2. The individual does not have any neuropathic symptoms (e.g. convulsive crisis, ataxia, dementia, swallowing difficulties);

3. ONE of the following:

   1. The individual is 2 years of age or older and request is for Cerezyme ((imiglucerase);

   2. The individual is 4 years of age or older and request is for Elelyso (taliglucerase) or Vpriv (velaglucerase);

4. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

5. The individual has glucocerebrosidase activity of <15% of mean normal in fibroblasts, leukocytes, or other nucleated cells OR the individual has genetic analysis with disease causing mutations on 2 alleles of glucocerebrosidase genome;

6. The individual has ONE of the following:

   1. Anemia defined as mean hemoglobin level below the testing laboratory’s lower limit of normal based on age and gender;

   2. Platelet count of <100,000 µL on at least 2 measurements; 

   3. Hepatomegaly; 

   4. Splenomegaly;

   5. Growth velocity below the standard mean for age; 

   6. Evidence of bone disease with other causes ruled out;

7. The provider has documented current levels of the following: hemoglobin levels, platelet count, liver and spleen volumes, status of bone pain, and individual's growth velocity if applicable;

8. The individual is not currently taking another enzyme replenisher and will not start therapy with another enzyme replenisher;

9. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Initial Request: Cerdelga (eliglustat)

The requested medication may be considered medically necessary when ALL of the following criteria are met:

1. The individual has a diagnosis of Gaucher disease Type 1;

2. The individual is 18 years of age or older;

3. The individual is confirmed to be a CYP2D6 extensive metabolizer (EM), intermediate metabolizer (IM), or poor metabolizer (PM) as detected by an FDA-cleared test;

4. The individual is not currently taking another enzyme replenisher and will not start therapy with another enzyme replenisher;

5. The individual does not have any FDA-labeled contraindication(s) to Cerdelga (eliglustat);

6. BOTH of the following:

   1. The individual has no pre-existing cardiac disease (i.e., congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia, long QT syndrome, etc.);

   2. The individual is not taking a Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) anitarrhythmic medication;

7. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g., endocrinologist, geneticist, hematologist);

8. The prescribed dosage is within the FDA labeled dose range (see below).

Length of Approval: 12 months

Initial Request: Zavesca (miglustat)

Miglustat may be considered medically necessary when ALL of the following criteria are met:

1. The individual is 18 years of age or older;

2. The individual has a diagnosis of Gaucher disease Type 1;

3. ONE of the following:

   1. The individual has a documented allergy or hypersensitivity to enzyme replacement therapy,

   2. The individual has clinical documentation of poor venous access ruling out the option of enzyme replacement therapy;

4. The requested dosage is within the FDA-labeled dose range.

5. The individual is not currently taking another enzyme replenisher and will not start therapy with another enzyme replenisher;

6. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g., endocrinologist, geneticist, hematologist).

Length of Approval: 12 months

Renewal Criteria: Cerezyme (imiglucerase), Elelyso (taliglucerase), VPRIV (velaglucerase), Cerdelga (eliglustat), Zavesca (miglustat)

The requested agent may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has previously been approved for the requested agent through the BCBSMS PA process;

2. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g., endocrinologist, geneticist, hematologist);

3. The prescriber has provided documentation to show improvement or stabilization of ONE of the following:

   1. Hemoglobin levels

   2. Platelet count sufficient to decrease the risk of bleeding

   3. Liver or spleen volumes

   4. Growth

   5. Bone pain

4. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Mucopolysaccaridosis

Initial Request: Aldurazyme (laronidase), Elaprase (idursulfase), Naglazyme (galsulfase)

The requested medication may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The request is for Aldurazyme (laronidase) and ALL of the following:

      1. The individual is 6 months of age or older;

      2. The individual has a diagnosis of Hurler, Hurler-Scheie or Scheie Syndrome [Mucopolysaccharidosis type I (MPS I)];

      3. ONE of the following:

         1. The individual has α-L-iduronidase enzyme activity that is <10% of average reference values in leukocytes, fibroblasts, plasma or serum and has normal enzyme activity in at least one other sulfatase enzyme;

         2. The individual has genetic analysis with disease causing mutation of the α-L-iduronidase gene;

   2. The request is for Elaprase (idursulfase) and ALL of the following:

      1. The individual is 16 months of age or older;

      2. The individual has a diagnosis of Hunter Syndrome [Mucopolysaccharidosis type II (MPS II)];

      3. ONE of the following:

         1. The individual has an iduronate-2-sulfatase deficiency in leukocytes, fibroblasts, or plasma and has a normal enzyme activity in at least one other sulfatase enzyme;

         2. The individual has genetic analysis of disease causing mutation of the iduronate 2-sulfatase gene;

   3. The request is for Naglazyme (galsulfase) and ALL of the following:

      1. The individual is 3 months of age or older;

      2. The individual has a diagnosis of Maroteaux-Lamy Syndrome [Mucopolysaccharidosis type VI (MPS IV)];

      3. ONE of the following:

         1. The individual has an arylsulfatase B enzyme activity of <10% of the lower limit of normal in cultured fibroblasts and has normal enzyme activity in at least one other sulfatase enzyme; 

         2. The individual has genetic analysis with disease causing mutation in the arylsulfatase B gene;

2. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

3. ONE of the following:

   1. In an overnight sleep study the individual has had either an average of >5 apnea events per hours (>1 apnea event per hour for children) over the individual's total sleep OR more than 2 severe episodes of desaturation (mean nocturnal O2 saturation of <85% in adults; <92% in children);.

   2. The individual has a forced vital capacity (FVC) <80% predicted value for height;

   3. The individual has reduced ejection fraction of <56% (normal range 56-78%);

   4. The individual has a reduction in fraction shortening to <25% (normal range 25-46%);

   5. The individual has restricted range of movement in joints of >10° from normal; 

   6. The individual has splenomegaly;

   7. The individual has hepatomegaly;

4. The prescriber has documented current levels for joint mobility, walking capacity, ejection fraction, forced vital capacity, liver and spleen volumes, (and if applicable sleep apnea/desaturation sleep study results);

5. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Renewal Criteria: Aldurazyme (laronidase), Elaprase (idursulfase), Naglazyme (galsulfase)

The requested medication may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has previously been approved for the requested agent through the BCBSMS PA process;

2. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

3. The prescriber has provided documentation to show improvement in or stabilization of ONE of the following:

   1. Joint mobility;

   2. Walking capacity;

   3. Ejection fraction;

   4. Fraction shortening;

   5. Forced vital capacity;

   6. Liver or spleen volume;

   7. Sleep apnea/severity of desaturation episodes;

4. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Other Lysosomal Storage Disorders

Initial Request: Fabrazyme (agalsidase)

Fabrazyme (agalsidase) may be considered medically necessary when ALL of the following criteria are met:

1. The individual is 8 years of age or older;

2. The individual has a diagnosis of Fabry disease;

3. ONE of the following:

   1. The individual is male and has a deficiency in alpha-galactosidase A (alpha-Gal A) activity in leukocytes, fibroblasts, or plasma OR

   2. The individual has a diagnosis based on mutation of the alpha-Gal A gene;

4. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

5. The prescriber has assessed current levels of ALL of the following:

   1. Kidney function (proteinuria, GFR);

   2. Cardiac function (left ventricular hypertrophy, conduction or rhythm, mitral or aortic insufficiency);

   3. Optic neuropathy;

   4. Neuropathic pain;

   5. Gastrointestinal symptoms;

6. The individual is not currently being treated with Galafold (migalastat) or if currently being treated with Galafold (migalastat) will discontinue prior to starting the requested agent;

7. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Renewal Criteria: Fabrazyme (agalsidase)

Fabrazyme (agalsidase) may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has previously been approved for the requested agent through the BCBSMS PA process; 

2. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

3. The prescriber has provided documentation to show improvement in or stabilization of ONE of the following:

   1. Kidney function (proteinuria, GFR);

   2. Cardiac function (left ventricular hypertrophy, conduction of rhythm, mitral or aortic insufficiency;

   3. Optic neuropathy;

   4. Neuropathic pain;

   5. Gastrointestinal symptoms;

4. The individual is not currently being treated with Galafold (migalastat) or if currently being treated with Galafold (migalastat) will discontinue prior to starting the requested agent.

5. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Elfabrio (pegunigalsidase alfa) is considered not medically necessary as there are other formulary alternatives covered by the Plan for the treatment of Fabry disease. 

Initial Request: Kanuma (sebelipase alfa)

Kanuma (sebelipase alfa) may be considered medically necessary when ALL of the following criteria are met:

1. The individual is 1 month of age or older;

2. The individual has a Lysosomal Acid Lipase Deficiency (LAL-D) as diagnosed by ONE of the following:

   1. Dried Blood Spot (DBS) testing;

   2. Genetic analysis with the disease-causing mutations on the LIPA gene;

   3. Measurement of lysosomal acid lipase activity in peripheral blood mononuclear cells or cultured fibroblasts;

3. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

4. If the individual has the cholesteryl ester storage disease variant (CESD), then ONE of the following:

   1. The individual has failed maximally tolerated statin therapy;

   2. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL statins;

5. The prescriber has documented current levels of growth (if applicable), lipid levels (LDL, TG, non-HDL, HDL), and liver volume;

6. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Renewal Criteria:Kanuma (sebelipase alfa)

Kanuma (sebelipase alfa) may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has previously been approved for the requested agent through the BCBSMS PA process;

2. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

3. The prescriber has provided documentation to show improvement in or stabilization of ONE of the following:

   1. Growth;

   2. Lipid levels (LDL, TG, non-HDL, HDL);

   3. Liver volume;

4. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Pompe Disease

Initial Request: Lumizyme (alglucosidase), Nexviazyme (avalglucosidase alfa-ngpt), Pombiliti (cipaglucosidase alfa-atga) in combination with Opfolda (miglustat)

Lumizyme (alglucosidase), Nexviazyme (avalglucosidase alfa-ngpt), or Opfolda (miglustat)/Pombiliti (cipaglucosidase alfa-atga) may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The individual is 1 week of age or older and the request is for Lumizyme (alflucosidase);

   2. The individual is 1 year of age or older and the request is for Nexviazyme (avalglucosidase alfa-ngpt);

   3. The individual is 18 years of age or older and the request is for Pombiliti (cipaglucosidase alfa-atga) in combination with Opfolda (miglustat), AND documentation supports that the individual is not improving on current therapy;

2. The individual has been diagnosed with Pompe disease (an acid alpha-glucosidase [GAA] deficiency) by ONE of the following:

   1. Prenatal diagnosis via chorionic villus biopsies and/or cultured amniotic cells;

   2. Genetic testing confirming two pathogenic mutations on separate alleles in the GAA gene;

   3. Diagnosis by TWO of the following:

      1. Dried blot spot enzyme assay;

      2. Skin fibroblast enzyme assay;

      3. Lymphocytes;

      4. Mixed leukocytes;

      5. Urinary tetrasaccharides;

      6. Skeletal muscle biopsy;

3. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

4. The individual is not receiving invasive ventilation due to respiratory failure;

5. The prescriber has evaluated current status of ONE or more of the following:

   1. Gross motor function (e.g. PEDI-Pompe scale);

   2. Swallowing (e.g. videofluoroscopy);

   3. Neurological function;

   4. Pulmonary function (e.g. FVC % predicted);

   5. Liver or spleen volumes;

   6. Growth (if applicable);

   7. Cardiac function (e.g. cardiomyopathy);

6. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

Renewal Criteria:Lumizyme (alglucosidase), Nexviazyme (avalglucosidase alfa-ngpt), Pombiliti (cipaglucosidase alfa-atga) in combination with Opfolda (miglustat)

Lumizyme (alglucosidase), Nexviazyme (avalglucosidase alfa-ngpt), or Pombiliti (cipaglucosidase alfa-atga) in combination with Opfolda (miglustat) may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has previously been approved for the requested agent through the BCBSMS PA process;

2. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g. endocrinologist, geneticist, hematologist);

3. The prescriber has provided documentation to show improvement in or stabilization of ONE of the following:

   1. Gross motor function (e.g. PEDI-Pompe scale);

   2. Swallowing (e.g. videofluoroscopy);

   3. Neurological function;

   4. Pulmonary function (e.g. FVC % predicted);

   5. Liver or spleen volumes;

   6. Growth;

   7. Cardiac function;

4. The individual is not receiving invasive ventilation due to respiratory failure;

5. The dose requested is within the FDA-labeled dose range.

Length of Approval: 12 months

POLICY EXCEPTIONS

State Health Plan (State and School Employees):The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary. BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

BCBSMS determines member medication trial and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and to submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

03/26/2019: New policy added. Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

07/28/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy updated to include approval criteria for Cerdelga (eliglustat) and Zavesca (miglustat). Revised policy statement criteria for Cerezyme, Elelyso, Vpriv, Lumizyme, and Elaprase. Policy Guidelines updated to define medication failure. Sources updated.

11/01/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated. Policy statement criteria updated for patients with Gaucher disease Type 1 and other lysosomal storage disorders. Added medically necessary criteria for patients with mucopolysaccaridosis. Policy Exceptions updated for State Health Plan members. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders." Added information regarding BCBSMS request for medical records. Sources updated. Code Reference updated to add HCPCS codes J0180, J0221, J1458, J1743, J1786, J1931, J2840, J3060, and J3385.

04/15/2022: Policy updated to add Nexviazyme (avalglucosidase alfa-ngpt). Policy section and Policy Guidelines updated to change "patient" to "member." Initial and renewal request criteria for Pompe disease updated to add Nexviazyme (avalglucosidase alfa-ngpt) as medically necessary when meeting the specified conditions. Sources updated. Code Reference section updated to add HCPCS code J0219.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

10/01/2024: Policy updated to add Elfabrio (pegunigalsidase alfa), Opfolda (miglustat), and Pombiliti (cipaglucosidase alfa-atga). Policy statements updated to change "member" to "individual." Added policy statement that Elfabrio (pegunigalsidase alfa) is considered not medically necessary as there are other formulary alternatives covered by the Plan for the treatment of Fabry disease. Policy statements for initial and renewal requests for Pompe Disease updated to add Opfolda (miglustat)/Pombiliti (cipaglucosidase alfa-atga) as medically necessary/approved if the listed criteria are met. Policy Guidelines updated to remove investigative definition. Sources updated. Code Reference section updated to add HCPCS codes J1202 and J1203 to the Medically Necessary Codes table and HCPCS code J2508 to the Not Medically Necessary Codes table. Effective 12/01/2024.

06/03/2025: Policy reviewed by Pharmacy & Therapeutics (P&T) Committee; no changes.

SOURCE(S)

1. Aldurazyme prescribing information. Genzyme Corporation. December 2019. Last accessed August 2020.

2. Cerdelga prescribing information. Genzyme Corporation. August 2018. Last accessed August 2020.

3. Cerezyme prescribing information. Genzyme. March 2020. Last accessed August 2020.

4. Elaprase prescribing information. Shire US Manufacturing Inc. November 2018. Last accessed August 2020.

5. Elelyso prescribing information. Pfizer. October 2019. Last accessed August 2020.

6. Elfabrio prescribing information. Chiesi USA, Inc. March 2024. Last accessed March 2024.

7. Fabrazyme prescribing information. Genzyme Corporation. December 2018. Last accessed August 2020.

   https://emedicine.medscape.com/article/944157

8. Kanuma prescribing information. Alexion Pharmaceuticals, Inc. December 2015. Last accessed August 2020.

9. Lumizyme prescribing information. Genzyme Corporation. February 2020. Last accessed August 2020.

10. Miglustat prescribing information. ANI Pharmaceuticals, Inc. August 2019. Last accessed August 2020.

11. Naglazyme prescribing information. BioMarin Pharmaceutical Inc. December 2019. Last accessed August 2020.

12. Nexviazyme prescribing information. Genzyme Corporation. August 2021. Last accessed June 2022.

13. Opfolda prescribing information. AMICUS THERAPEUTICS US, LLC. October 2023. Last accessed April 2024.

14. Pombiliti prescribing information. AMICUS THERAPEUTICS US, LLC. October 2023. Last accessed May 2024.

15. Vpriv prescribing information. Shire. November 2019. Last accessed August 2020.

16. Zavesca prescribing information. Actelion Pharmaceuticals US, Inc. April 2023. Last accessed April 2024.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

Not Medically Necessary Codes

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