Enzyme Replacement Therapies

Policy ID: I-58-034

Section: Injections

Effective Date: July 01, 2018

Revised Date: March 11, 2024

Revision Effective Date: April 01, 2024

Last Reviewed: March 19, 2024

Applies To: Commercial Only

Description

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®), avalglucosidase alfa-ngpt (Nexviazyme ^TM ) and cipaglucosidase alfa-atga (Pombiliti ^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.

Velmanase alfa-tycv (Lamzede®) is a recombinant human lysosome that provides an exogenous source of alpha mannidosidase in those who have reduced activity of this enzyme (alpha-mannosidosis). Alpha mannosidase catalyzes the degradation of accumulated mannose-containing oligosaccharides. Velmanase alfa-tycv binds to the mannose-6-phosphate receptor on the cell surface and transports into lysosomes where it is thought to exert enzyme activity.

Policy Application

All claims submitted for this policy will be processed according to the policy effective date and associated revision effective dates in effect on the date of service.

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

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

Individuals two (2) 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 one (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.

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.

The use of agalsidase beta (Fabrazyme) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J0180

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

ONE of the following:
- The prescriber states the individual has been treated with pegunigalsidase alfa-iwxj (Elfabrio) (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed; or
- ONE of the following:
  - The individual has tried and had an inadequate response, has an intolerance, or has a hypersensitivity to agalsidase beta (Fabrazyme); or
  - The patient has an FDA labeled contraindication to agalsidase beta (Fabrazyme); and
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.

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
ONE of the following:
- The prescriber states the individual has been treated with pegunigalsidase alfa-iwxj (Elfabrio) (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed; or
- ONE of the following:
  - The individual has tried and had an inadequate response, has an intolerance, or has a hypersensitivity to agalsidase beta (Fabrazyme); or
  - The patient has an FDA labeled contraindication to agalsidase beta (Fabrazyme); and
Individual will not concomitantly be treated with migalastat.

The use of pegunigalsidase alfa-iwxj (Elfabrio) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J2508

Alglucosidase alfa (Lumizyme) may be considered medically necessary in individuals with infant-onset Pompe disease (GAA deficiency) when ONE 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 one (1)% of the normal mean (complete deficiency) associated with classic infantile onset Pompe disease; or a partial deficiency (two (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.

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).

The use of alglucosidase alfa (Lumizyme) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J0221

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 two (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).

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).

Procedure Code

J0221

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 (two (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.

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).

The use of avalglucosidase alfa-ngpt (Nexviazyme) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J0219

Cipaglucosidase alfa-atga (Pombiliti) and miglustat (Opfolda) may be considered medically necessary when ALL the following criteria are met:

Individual is 18 years of age or older; and
Confirmed diagnosis of late onset Pompe disease by documentation of either of the following:
- GAA enzyme deficiency; or
- GAA genotyping; and
Individual weighs greater than or equal to 40kg; and
Individual is receiving ERT (Lumizyme or Nexviazyme) for at least 24 months with no improvement with last dose being two (2) weeks prior to initiation of cipaglucosidase alfa-atga; and
Individual has received miglustat (Opfolda) oral capsule one (1) hour before initiation of cipaglucosidase alfa-atga (Pombiliti) infusion.

Reauthorization Criteria

Continuation of cipaglucosidase alfa-atga (Pombiliti) and miglustat (Opfolda) for the treatment of Pompe disease may be considered medically necessary when ALL the following criteria are met:

Individual has documented positive clinical response (e.g. improvement in FVC, 6-minute walk distance (6MWD), muscle function, etc.); and
Continued therapy with cipaglucosidase alfa-atga (Pombiliti) is prescribed in combination with miglustat (Opfolda).

The use of cipaglucosidase alfa-atga (Pombiliti) and miglustat (Opfolda) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Codes

J1202

J1203

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.

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.

The use of elosulfase alfa (Vimizim) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J1322

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).

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.

The use of galsulfase (Naglazyme) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J1458

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) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J1743

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.

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.

The use of laronidase (Aldurazyme) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J1931

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.

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.

The use of sebelipase alfa (Kanuma) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J2840

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.

Reauthorization Criteria

Continuation 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.

The use of vestronidase alpha-vjbk (Mepsevii) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J3397

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
Clinical 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.

Reauthorization

Continuation therapy with olipudase alfa-rpcp (Xenpozyme) 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 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).

The use of olipudase alfa-rpcp (Xenpozyme) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J0218

Velmanase alfa-tycv (Lamzede) may be considered medically necessary for adult and pediatric individuals when ALL following criteria are met:

Individual has confirmed diagnosis alpha-Mannosidosis as defined by alpha-Mannosidase activity less than 10% of normal activity; and
Treatment is utilized for non-central nervous system manifestations (e.g., mobility, lung function); and
Initial authorization will be for a period of 12 months.

Reauthorization Criteria

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

Individual is established on therapy with velmanase alfa-tycv (Lamzede); and
Provider attestation that individual has demonstrated disease stability or beneficial response to therapy from baseline (e.g. reduction in serum oligosaccharides, improvement in 3-minute stair climbing test (3MSCT), 6-minute walking test (6MWT) or forced vital capacity (FVC) (% predicted)); and
Reauthorization will be for a period of 12 months.

The use of velmanase alfa-tycv (Lamzede) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J0217

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the United States Food and Drug Administration (U.S. FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines.

Diagnosis Codes

Covered Diagnosis Code for J0180 and J2508

E75.21

Covered Diagnosis Code for J0219, J0221, J1202, J1203

E74.02

Covered Diagnosis Code for J1322

E76.210

Covered Diagnosis Codes for J1458

E76.29

E76.3

Covered Diagnosis Code for J1743

E76.1

Covered Diagnosis Codes for J1931

E76.01

E76.02

E76.03

Covered Diagnosis Code for J2840

E75.5

Covered Diagnosis Code for J3397

E76.29

Covered Diagnosis Codes for J0218

E75.241

E75.244

E75.249

Professional Statements and Societal Positions Guidelines

Not Applicable

ND Committee Review

Internal Medical Policy Committee 5-2019 Annual Review

Internal Medical Policy Committee 3-16-2020 Annual Review

Internal Medical Policy Committee 3-17-2021 Annual review, no clinical content change

Internal Medical Policy Committee 3-23-2022 - Effective April 01, 2022

Added precertification drug avalglucosidase alfa-ngpt (Nexviazyme) to the policy,
Updated the title of the policy,
Added reauthorization criteria for alglucosidase alfa (Lumizyme)

Internal Medical Policy Committee 5-24-2022

Changed policy name, and
Added idursulfase (Elaprase), sebelipase alfa (Kanuma), elosulfase alfa (Vimizim), galsulfase (Naglazyme) vestronidae alpha-vjbk (Mepsevii), laronidase (Aldurazyme) or agalsidase beta (Fabrazyme) to the policy and
Archived single name policies, I-93; I-178; I-138; I-140; I-188; I-54, I-55; and
Updated the experimental/investigational statement.

Internal Medical Policy Committee 11-29-2022 - Effective December 1, 2022

Added precertification drug olipudase alfa-rpcp (Xenpozyme) to the policy, and
Updated avalglucosidase alfa-ngpt (Nexviazyme) criteria; and
Updated experimental/investigational statement

Internal Medical Policy Committee 3-23-2023 Effective April 01, 2023

Added new code, J0218 olipudase alfa-rpcp (Xenpozyme), to the policy

Internal Medical Policy Committee 9-12-2023 - Effective October 01, 2023

Added precertification drug pegunigalsidase alfa-iwxj (Elfabrio) to the policy

Internal Medical Policy Committee 11-15-2023 - Effective January 01, 2024

Added new code J2508 for pegunigalsidase alfa-iwxj (Elfabrio)

Internal Medical Policy Committee 1-16-2024 - Effective March 01, 2024

Added cipaglucosidase alfa-atga (Pombiliti) as always E/I; and
Added velmanase alfa-tycv (Lamzede) as a precertification drug; and
Updated age for agalsidase beta (Fabrazyme) from eight (8) to two (2)

Internal Medical Policy Committee 3-19-2024 - Effective April 01, 2024

Added criteria for cipaglucosidase alfa-atga (Pombiliti) and miglustat (Opfolda); and
Added new codes J1202; and J1203; and
Added trial of agalsidase beta (Fabrazyme) to pegunigalsidase alfa-iwxj (Elfabrio) criteria

Links

References (PDF)

Disclaimer

Current medical policy is to be used in determining a Member's contract benefits on the date that services are rendered. Contract language, including definitions and specific inclusions/exclusions, as well as state and federal law, must be considered in determining eligibility for coverage. Members must consult their applicable benefit plans or contact a Member Services representative for specific coverage information. Likewise, medical policy, which addresses the issue(s) in any specific case, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and the Company reserves the right to review and update medical policy periodically.

Policy ID: I-58-033

Section: Injections

Effective Date: July 01, 2018

Revised Date: January 10, 2024

Revision Effective Date: March 01, 2024

Last Reviewed: January 16, 2024

Archived Date: March 31, 2024

Applies To: Commercial Only

Description

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

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

Individuals two (2) 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 one (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.

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.

Procedure Code

J0180

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.

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.

Procedure Code

J2508

Alglucosidase alfa (Lumizyme) may be considered medically necessary in individuals with infant-onset Pompe disease (GAA deficiency) when ONE 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 one (1)% of the normal mean (complete deficiency) associated with classic infantile onset Pompe disease; or a partial deficiency (two (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.

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).

Procedure Code

J0221

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 two (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).

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).

Procedure Code

J0221

Diagnosis of late-onset Pompe disease based on:
- GAA enzyme assay which shows reduced enzyme activity (two (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.

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).

Procedure Code

J0219

Cipaglucosidase alfa-atga (Pombiliti) is considered experimental/investigational and therefore non-covered as there is a lack of conclusive evidence confirming clinical efficacy.

Procedure Code

J3590

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.

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.

Procedure Code

J1322

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).

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.

Procedure Code

J1458

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.

Procedure Code

J1743

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.

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.

Procedure Code

J1931

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.

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.

Procedure Code

J2840

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.

Reauthorization Criteria

Continuation 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.

Procedure Code

J3397

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
Clinical 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.

Reauthorization

Continuation therapy with olipudase alfa-rpcp (Xenpozyme) 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 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).

Procedure Code

J0218

Velmanase alfa-tycv (Lamzede) may be considered medically necessary for adult and pediatric individuals when ALL following criteria are met:

Individual has confirmed diagnosis alpha-Mannosidosis as defined by alpha-Mannosidase activity less than 10% of normal activity; and
Treatment is utilized for non-central nervous system manifestations (e.g., mobility, lung function); and
Initial authorization will be for a period of 12 months.

Reauthorization Criteria

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

Individual is established on therapy with velmanase alfa-tycv (Lamzede); and
Provider attestation that individual has demonstrated disease stability or beneficial response to therapy from baseline (e.g. reduction in serum oligosaccharides, improvement in 3-minute stair climbing test (3MSCT), 6-minute walking test (6MWT) or forced vital capacity (FVC) (% predicted)); and
Reauthorization will be for a period of 12 months.

Procedure Code

J3590

Diagnosis Codes

Covered Diagnosis Code for J0180

E75.21

Covered Diagnosis Code for J0219 and J0221

E74.02

Covered Diagnosis Code for J1322

E76.210

Covered Diagnosis Codes for J1458

E76.29

E76.3

Covered Diagnosis Code for J1743

E76.1

Covered Diagnosis Codes for J1931

E76.01

E76.02

E76.03

Covered Diagnosis Code for J2840

E75.5

Covered Diagnosis Code for J3397

E76.29

Covered Diagnosis Codes for J0218

E75.241

E75.244

E75.249

Professional Statements and Societal Positions Guidelines

Not Applicable

ND Committee Review

Internal Medical Policy Committee 5-2019 Annual Review

Internal Medical Policy Committee 3-16-2020 Annual Review

Internal Medical Policy Committee 3-17-2021 Annual review, no clinical content change

Internal Medical Policy Committee 3-23-2022 - Effective April 01, 2022

Added precertification drug avalglucosidase alfa-ngpt (Nexviazyme) to the policy,
Updated the title of the policy,
Added reauthorization criteria for alglucosidase alfa (Lumizyme)

Internal Medical Policy Committee 5-24-2022

Changed policy name, and
Added idursulfase (Elaprase), sebelipase alfa (Kanuma), elosulfase alfa (Vimizim), galsulfase (Naglazyme) vestronidae alpha-vjbk (Mepsevii), laronidase (Aldurazyme) or agalsidase beta (Fabrazyme) to the policy and
Archived single name policies, I-93, I-178, I-138, I-140, I-188, I-54, I-55, and
Updated the experimental/investigational statement

Internal Medical Policy Committee 11-29-2022 - Effective December 1, 2022

Added precertification drug olipudase alfa-rpcp (Xenpozyme) to the policy, and
Updated avalglucosidase alfa-ngpt (Nexviazyme) criteria
Updated experimental/investigational statement

Internal Medical Policy Committee 3-23-2023 Effective April 01, 2023

Added new code, J0218 olipudase alfa-rpcp (Xenpozyme), to the policy

Internal Medical Policy Committee 9-12-2023 - Effective October 01, 2023

Added precertification drug pegunigalsidase alfa-iwxj (Elfabrio) to the policy

Internal Medical Policy Committee 11-15-2023 - Effective January 01, 2024

Added new code J2508 for pegunigalsidase alfa-iwxj (Elfabrio)

Internal Medical Policy Committee 1-16-2024 - Effective March 01, 2024

Added cipaglucosidase alfa-atga (Pombiliti) as always E/I
Added velmanase alfa-tycv (Lamzede) as a precertification drug
Updated age for agalsidase beta (Fabrazyme) from eight (8) to two (2)

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