Agalsidase beta (Fabrazyme®) and pegunigalsidase alfa-iwxj Elfabrio® are an exogenous source of the lysosomal enzyme α-glucosidase A (a-GalA), catalyzing the hydrosis of glycosphinogolipids, including globotriaosylceramide (GL-3), hence reducing its deposition in capillary endothelium of the kidney, heart, brain and other tissue types. α-glucosidase A deficiency, otherwise known as Fabry Disease, is an X- linked genetic disorder of glycosphingolipid metabolism. Deficiency of a-Gal leads to progressive accumulation of glycoshingolipids, predominantly GL-3, in many body tissues, occurring over a period of years. Clinical manifestations of the disease include renal failure, cardiomyopathy and cerebrovascular accidents.

Alglucosidase alfa (Lumizyme®) and avalglucosidase alfa-ngpt (Nexviazyme^TM)  are enzyme replacements used for specific indications as a treatment of Pompe disease. Pompe disease (glycogen storage disease type II, GSDII, glycogenosis type II, acid maltase deficiency) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of acid alpha-glucosidase (GAA), an enzyme that degrades lysosomal glycogen.  

Elosulfase alfa (Vimizim^TM) is a purified human enzyme produced by recombinant DNA for the treatment of Mucopolysaccharidosis type IVA (MPS IVA) or Morquio A syndrome which causes a deficiency in N-acetylgalactosamine-6-sulfatase (GALNS).  Elosulfase alfa (Vimizim) replaces the missing enzyme GALNS.

Galsulfase (Naglazyme®) is a human enzyme produced by recombinant DNA technology in a Chinese hamster ovary. Galsulfase is an orphan drug used to treat the inherited metabolic disorder mucopolysaccharidosis VI (MPS VI or Maroteaux-Lamy Syndrome). MPS VI is caused by a lack of the enzyme ASB that normally breaks down certain carbohydrates known as glycosaminoglycans. MPS VI causes widespread cumulative organ and tissue damage.

Idursulfase (Elaprase^®), is a purified form of human iduronate-2-sulfatase used for the treatment of Hunter syndrome (Mucopolysaccharidosis II, MPS II) a rare, genetic disease which can lead to premature death. Hunter syndrome is characterized by glycosaminoglycan accumulation due to deficiency in the enzyme iduronate 2-sulfase, which is needed to adequately break down complex sugars produced in the body. Hunter syndrome usually becomes apparent in children one (1) to three (3) years of age.

Sebelipase alfa (Kanuma®) is a recombinant human lysosomal acid lipase (rhLAL). Lysosomal acid lipase  is a lysosomal glycoprotein enzyme that catalyzes the hydrolysis of cholesteryl esters to free cholesterol and fatty acids and the hydrolysis of triglycerides to glycerol and free fatty acids.

Vestronidase alpha-vjbk (Mepsevii^TM) is a recombinant human lysosomal beta glucuronidase enzyme replacement therapy indicated in pediatric and adult individuals for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).MPS VII is caused by pathogenic mutations in the GUSB gene. The GUSB gene is responsible for producing an enzyme called beta-glucuronidase which is involved in the breakdown of large molecules called glycosaminoglycans (GAGs).

Laronidase (Aldurazyme®) is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme used to treat mucopolysaccharidosis I (MPS I), an autosomal recessive disorder which causes a deficiency of alpha-L-iduronidase, an enzyme required to break down glycosaminoglycans.

Olipudase alfa-rpcp (Xenpozyme^TM) is a hydrolytic lysosomal sphingomyelin-specific enzyme indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD), a lysosomal storage disease. ASM is necessary to break down the fatty substance shingomyelin in the lysosomes. Buildup of sphingomyelin can occur in major organs such as the liver, lungs, and spleen which, over time, can cause serious health complications. 

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

• Individuals eight (8) years of age or older with a confirmed diagnosis of Fabry disease made by ONE of the following methods:
  • For male individuals: documentation of complete deficiency or less than 1% of mean normal alpha-galactosidase A (α-Gal A) enzyme activity in leukocytes, dried blood spots, or serum (plasma) analysis; or
  • For female individuals: documented galactosidase alpha gene (GLA) mutation by gene sequencing; and
• At least ONE of the following signs and symptoms:
  • Angiokeratomas (clusters of small, dark red spots on the skin); or
  • Acroparesthesias (episodes of pain, particularly in the hands and feet); or
  • Corneal verticillata (whorls); or
  • Corneal opacity; or  
  • Personal or family history of exercise, heat, or cold intolerance; or
  • Decreased sweating (anhidrosis or hypohidrosis); or
  • Personal or family history of renal failure; or
  • Hearing manifestations (tinnitus); and
• The medication is prescribed by or in consultation with a physician who specializes in the treatment of inherited metabolic disorders; and
• Individual will not concomitantly be treated with migalastat; and
• Initial authorization will be for 12 months.

Reauthorization Criteria

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

• Individual diagnosed with Fabry disease; and
• Provider attestation that individual has demonstrated disease stability or beneficial response to therapy; and
• Individual will not concomitantly be treated with migalastat; and
• Reauthorization is for 12 months.

The use of agalsidase beta (Fabrazyme) not meeting the criteria as indicated in this policy is considered not medically necessary.

Pegunigalsidase alfa-iwxj (Elfabrio) may be considered medically necessary when ALL the following criteria are met:

• Individuals 18 years of age or older with a confirmed diagnosis of Fabry disease made by ONE of the following methods:
  • For male individuals: documentation of complete deficiency or less than 1% of mean normal alpha-galactosidase A (α-Gal A) enzyme activity in leukocytes, dried blood spots, or serum (plasma) analysis; or
  • For female individuals: documented galactosidase alpha gene (GLA) mutation by gene sequencing; and
• Symptomatic Fabry disease which includes at least ONE of the following:
  • Angiokeratomas (clusters of small, dark red spots on the skin); or
  • Acroparesthesias (episodes of pain, particularly in the hands and feet); or
  • Corneal verticillata (whorls); or
  • Corneal opacity; or  
  • Personal or family history of exercise, heat, or cold intolerance; or
  • Decreased sweating (anhidrosis or hypohidrosis); or
  • Personal history of progressive renal failure, renal insufficiency or proteinuria; or
  • Hearing manifestations (tinnitus); and
• The medication is prescribed by or in consultation with a physician who specializes in the treatment of inherited metabolic disorders; and
• Individual will not concomitantly be treated with migalastat; and
• Initial authorization will be for 12 months.

Reauthorization Criteria

Reauthorization of pegunigalsidase alfa-iwxj (Elfabrio) may be considered medically necessary when ALL of the following criteria are met:

• Individual diagnosed with Fabry disease; and
• Provider attestation that individual has demonstrated disease stability or beneficial response to therapy; and
• Individual will not concomitantly be treated with migalastat; and
• Reauthorization is for 12 months.

The use of pegunigalsidase alfa-iwxj (Elfabrio) not meeting the criteria as indicated in this policy is considered not medically necessary.

Alglucosidase alfa (Lumizyme®) may be considered medically necessary in individuals with infant-onset Pompe disease (GAA deficiency) when ALL of the following are met:

• Confirmed diagnosis of infantile-onset Pompe disease with acid alpha-glucosidase deficiency (GAA) activity in skin fibroblasts of less than 1% of the normal mean (complete deficiency) associated with classic infantile onset Pompe disease; or a partial deficiency (2% to 40% of normal controls) of GAA enzyme activity associated with the non-classic infantile onset and late onset forms; or 
• GAA gene testing; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of alglucosidase alfa (Lumizyme) for the treatment of Pompe disease may be considered medically necessary when the initial criteria are met and the individual has documented positive clinical response (e.g. improvement in muscle function and mobility); and
• Reauthorization will be for a period of 12 months.

The use of alglucosidase alfa (Lumizyme) not meeting the criteria as indicated in this policy is considered not medically necessary.

Alglucosidase alfa (Lumizyme) may also be considered medically necessary for individuals with juvenile and late-onset Pompe disease (GAA deficiency) when ALL of the following are met:

• Diagnosis of Pompe disease based on:
  • GAA enzyme assay which shows reduced enzyme activity 2% to 40% partial deficiency of GAA non-classic infantile forms or late onset forms) of the lab specific normal mean value; and
  • Confirmed by ANY ONE of the following: 
    • A second GAA enzyme activity assay in a separate sample (from purified lymphocytes or fibroblast [minimally invasive test]; or
    • A muscle biopsy, [ invasive testing]); or
    • GAA gene testing; and
  • One or more clinical symptoms of Pompe disease are present such as: progressive muscle weakness, respiratory insufficiency is present. (Not an all-inclusive list); and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of alglucosidase alfa (Lumizyme) for the treatment of Pompe disease may be considered medically necessary when the initial criteria are met and the individual has documented positive clinical response (e.g. improvement in muscle function and mobility); and
• Reauthorization will be for a period of 12 month

The use of alglucosidase alfa (Lumizyme) not meeting the criteria as indicated in this policy is considered not medically necessary.

Avalglucosidase alfa-ngpt (Nexviazyme) may be considered medically necessary for individuals one (1) year of age and older with late-onset Pompe disease (GAA deficiency) when ALL of the following are met:

• Diagnosis of late-onset Pompe disease based on:
  • GAA enzyme assay which shows reduced enzyme activity (2% to 40% partial deficiency of the lab specific normal mean value); and
  • Confirmed by ANY ONE of the following: 
    • A second GAA enzyme activity assay in a separate sample (from purified lymphocytes or fibroblast [minimally invasive test]; or
    • A muscle biopsy, [ invasive testing]); or
    • GAA gene testing; and
  • Presence of ONE or more clinical signs and symptoms of Pompe disease such as (but not limited to):
    • Progressive muscle weakness; or
    • Delayed motor function; or
    • Respiratory Insufficiency; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

• Continuation of avalglucosidase alfa-ngpt (Nexviazyme) for the treatment of late-onset Pompe disease may be considered medically necessary when the initial criteria are met and the individual has documented positive clinical response (e.g. improvement in muscle function and mobility); and
• Reauthorization will be for a period of 12 months.

The use of avalglucosidase alfa-ngpt (Nexviazyme) not meeting the criteria as indicated in this policy is considered not medically necessary.

Elosulfase alfa (Vimizim) may be considered medically necessary for individuals five (5) years of age or older with a documented diagnosis of mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) defined as meeting ALL of the following criteria:

• Documented clinical signs and symptoms of the disease (e.g., kyphoscoliosis, corneal opacity, genu valgum, pectus carinatum, gait disturbance, growth deficiency.); and
• Documented reduced fibroblast or leukocyte GALNS enzyme activity or molecular genetic testing confirming diagnosis of MPS IVA; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

Continuation therapy with elosulfase alfa (Vimizim) may be considered medically necessary when ALL of the following criteria are met:

• Individual established on therapy; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy from baseline; and
• Reauthorization will be for a period of 12 months.

The use of elosulfase alfa (Vimizim) not meeting the criteria as indicated in this policy is considered not medically necessary.

Galsulfase (Naglazyme) may be considered medically necessary for the treatment of mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) when ALL of the following criteria are met:

• Absence or deficiency of fibroblast or leukocyte enzyme activity of N-acetylgalactosamine 4-sufatase (arylsulfatase B); or
• Molecular genetic confirmation of mutations in the ARSB gene; and
• Presence of clinical signs and symptoms of the disease (e.g., kyphoscolosis, genu valgum, pectus carinatum, gait disturbance, growth deficiency); and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

Continuation of therapy with galsulfase (Naglazyme) may be considered medically necessary for individuals diagnosed with MPS VI when ALL of the following criteria are met:

• Individual is established on therapy with galsulfase (Naglazyme); and
• Provider attestation that individual has demonstrated disease stability or beneficial response to therapy from baseline; and 
• Reauthorization will be for a period of 12 months. 

The use of galsulfase (Naglazyme) not meeting the criteria as indicated in this policy is considered not medically necessary.

Idursulfase (Elaprase) may be considered medically necessary for use in individuals with Hunter syndrome (Mucopolysaccharidosis II, MPS II) when the following criteria are met:

• Individual is five (5) years of age or greater; and
• Individual has demonstrated EITHER:
  • A deficiency of IDS enzyme activity in white blood cells (WBC), fibroblasts or plasma; or
  • Has hemizygous mutation in IDS gene; and
• Idursulfase (Elaprase) prescribed by or in consultation with a clinical geneticist, rheumatologist or hematologist.

Reauthorization Criteria

Continuation therapy with idursulfase (Elaprase) may be considered medically necessary when the following are met:

• Individual meets or previously met the above criteria; and
• Has decreased urinary glycosaminoglycans (uGAGS); or
• Has a positive clinical response indicated by an improvement of the previously reported laboratory values and symptoms.

The use of idursulfase (Elaprase) not meeting the criteria as indicated in this policy is considered not medically necessary.

Laronidase (Aldurazyme) may be considered medically necessary for individuals with ALL of the following:

• Diagnosis of ANY of the following forms of mucopolysaccharidosis type I confirmed by genetic testing or abnormal enzymology on cultured fibroblasts:
  • Hurler; or
  • Hurler-Scheie; or
  • Scheie form with moderate to severe symptoms; and

• Baseline predicted forced vital capacity (FVC); or
• Baseline distance walked in six (6) minutes; and
• Initial authorization will be for 12 months.

Reauthorization Criteria

Reauthorization of laronidase (Aldurazyme) may be considered medically necessary when ALL of the following criteria are met:

• Individual diagnosed with MPS I (Hurler, Hurler-Scheie or Scheie form as listed above); and
• Documentation of stability or improvement from baseline in FVC or distance walked in six (6) minutes; and
• Reauthorization is for 12 months.

The use of laronidase (Aldurazyme) not meeting the criteria as indicated in this policy is considered not medically necessary.

Sebelipase alfa (Kanuma) may be considered medically necessary for the treatment of lysosomal acid lipase (LAL) [Wolman’s disease, cholesteryl ester storage disease (CESD)] deficiency when ALL of the following criteria are met:

• Deficiency of LAL in peripheral blood leukocytes, fibroblasts, or dried blood spots; or
• Documented molecular genetic test revealing biallelic pathogenic variants (2) mutations in the LIPA gene; and
• Individual does not have severe liver cirrhosis (e.g., Child-Pugh class C); and
• Documentation of baseline weight for age Z-score for individuals with growth failure, and/or documentation of baseline LDL, HDL, AST, ALT and/or triglycerides; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

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

• No unacceptable adverse effect, e.g., anaphylaxis; and
• Treatment has resulted in a clinical benefit such as an improvement in weight for age Z-scores for individuals with growth failure, improved LDL, HDL, AST, ALT and/or triglycerides compared to previously submitted documentation; and
• Reauthorization will be for a period of 12 months.

The use of sebelipase alfa (Kanuma) not meeting the criteria as indicated in this policy is considered not medically necessary.

Vestronidase alpha-vjbk (Mepsevii) may be considered medically necessary in individuals ages five (5) months and older that meets ALL of the following criteria:

• Diagnosis of MPS VII (Sly syndrome) as confirmed by either:
  • Molecular genetic confirmation of pathogenic mutations in the GUSB gene; or
  • Decreased level of beta-glucuronidase activity in cultured leukocytes or fibroblasts; and
• Clinical signs and symptoms of MPS VII (e.g.,skeletal abnormalities shown on x-ray, short stature, macrocephaly, hepatosplenomegaly, etc); and
• Individual has increased level of urinary GAG; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

Continuation of therapy with vestronidase alfa (Mepsevii) may be considered medically necessary for individuals diagnosed with MPS VII when ALL of the following criteria are met:

• Individual is established on therapy with vestronidase alpha-vjbk (Mepsevii); and
• Provider attestation that individual has demonstrated disease stability or beneficial response to therapy from baseline; and
• Reauthorization will be for a period of 12 months.

The use of vestronidase alpha-vjbk (Mepsevii) not meeting the criteria as indicated in this policy is considered not medically necessary.

Olipudase alfa-rpcp (Xenpozyme) may be considered medically necessary for adult and pediatric individuals when ALL following criteria are met:

• Individual has confirmed diagnosis of ASMD as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes; and
• Cliinical diagnosis consistent with ASMD (Niemann-Pick Disease) Type B or A/B; and
• Individual has ALT or AST less than or equal to 250 IU/L or total bilirubin less than or equal to 1.5 mg/dL; and
• Female individual of childbearing age is not pregnant, confirmed by a negative serum pregnancy test; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

Continuation of therapy with olipudase alfa-rpcp (Xenpozyme) may be considered medically necessary for individuals diagnosed with ASMD when ALL of the following criteria are met:

• Individual is established on therapy with olipudase alfa-rpcp (Xenpozyme); and
• Provider attestation that individual has demonstrated disease stability or beneficial response to therapy from baseline (e.g. improvements in mean percent change in % predicted diffuse capacity of the lung for carbon monoxide (DLCO), spleen and liver volumes, and platelet counts); and
• Reauthorization will be for a period of 12 months.

The use of olipudase alfa-rpcp (Xenpozyme) not meeting the criteria as indicated in this policy is considered not medically necessary.

Enzyme replacement therapies in this policy  may be considered medically necessary for individuals 18 years of age and older when applicable clinical criteria for individual medication policies are met and when administered in a physician’s office not affiliated with a hospital, specialized infusion centers not affiliated with a hospital or in the home. 

Outpatient facility (Outpatient Hospital IV Infusion Department or Hospital-based Outpatient Clinical Level of Care) administration may be considered medically necessary if ANY of the following criteria are present to indicate the member is medically unstable for infusions in other than an outpatient facility setting:

• Member’s home is considered unsuitable for care by the home infusion provider; or
• Individual’s medical status requires enhanced monitoring beyond that which would routinely be needed for infusion therapy; or
• Previous severe adverse reaction (including but not limited to anaphylaxis, seizure, thromboembolism, myocardial infarction, renal failure) during or following administration of prescribed medication despite standard pre-medication; or
• Individual is receiving other medications that require close monitoring with a higher level of care (e.g., cytotoxic chemotherapy or blood products); or
• Individual is at high risk for complications due to medication administration (e.g., at risk for post-transplant complications, increased risk of infusion reactions due to presence of circulating antibodies, unstable vascular access, cardiopulmonary condition at risk for severe adverse reactions, unstable renal function with inability to safely tolerate IV volume loads, etc.); or 
• Individual is initiating therapy or re-initiating therapy after a period of at least 6 months with no therapy; or
• Physically and/or cognitively impaired AND a home caregiver is not available to comply with the required treatment regimen and schedule.

Home health services may be considered medically necessary when utilized for the administration of home infusion therapy and when provided by licensed eligible provider. Each case will be addressed on an individual basis.

The medications identified in this policy will be considered not medically necessary if administered in an unapproved hospital outpatient setting when an approved site of care is a viable option for treatment.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Evidence-based guidelines support the administration of injectable medications in alternative sites of care such as the non-hospital physician’s office, non-hospital infusion center or in the home.  Administration of the injectable medications subject to this policy at alternate sites of care is based upon the professional judgment of the provider, and takes into account the clinical appropriateness for each individual member. Requests for administration of any dose of alglucosidase alfa (Lumizyme), idursulfase (Elaprase)  sebelipase alfa (Kanuma), elosulfase alfa (Vimizim), galsulfase (Naglazyme), vestronidase alpha-vjbk (Mepsevii), laronidase (Aldurazyme), agalsidase beta (Fabrazyme), or olipudase alfa-rpcp (Xenpozyme) received from a hospital-based facility, physician’s office or specialized infusion center will be assessed for meeting the policy exception criteria based on the clinical documentation provided by the requesting practitioner.