CurrentunitedhealthcarePolicy CSIND0052.16

Medical Therapies for Enzyme Deficiencies (for Indiana Only)

State of Indiana-specific UnitedHealthcare medical benefit drug policy defining medical necessity criteria, initial and continuation authorization rules, and applicable HCPCS/ICD-10 codes for listed enzyme-replacement and related therapies for lysosomal and other enzyme deficiencies.

Policy Summary

Payerunitedhealthcare

PolicyMedical Therapies for Enzyme Deficiencies (for Indiana Only)

Policy CodePolicy CSIND0052.16

Change TypeRemoved therapies; code/diagnosis removals; updated clinical sections

Effective DateMar 1, 2026

Next Review Date

Key ActionInitial authorizations for all listed therapies are limited to no more than 12 months; prior authorization is required to determine medical necessity under the drug-specific criteria.

SourceLink

POLICY UPDATE CHANGES

Removed Lumizyme (alglucosidase alfa) and Nexviazyme (avalglucosidase alfa-ngpt) from the list of applicable medical therapies.

Replaced internal coverage contingency language for Lumizyme and Nexviazyme with requirement that coverage is contingent on state's Medicaid clinical policy.

Removed applicable HCPCS codes J0221 and J0219 from the policy's Applicable Codes section.

Removed ICD-10 diagnosis code E74.02 associated with Lumizyme and Nexviazyme from the policy.

Updated Background, Clinical Evidence, FDA, and References sections to reflect current information.

12Drugs Listed

12 monthsInitial authorization length (max)

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Policy scope (state)

2Removed therapies (Lumizyme, Nexviazyme)

1Policy revision date (most recent)

Coverage Summary

Key Policy Facts

Policy scope (state)Indiana

Drugs Listed12

Initial authorization length (max)12 months

Removed therapies2 (Lumizyme, Nexviazyme)

Policy revision date (most recent)03/01/2026

Initial and Continuation Therapy Criteria (by drug)

Aldurazyme (laronidase) - Initial and Continuation Therapy Criteria

Aldurazyme (laronidase) is medically necessary for the treatment of mucopolysaccharidosis I (MPS I) when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of any of the MPS I syndromes confirmed by one of the following: - Hurler variant (severe mucopolysaccharidosis I; also, MPS IH) - Hurler-Scheie variant (attenuated mucopolysaccharidosis I; also, MPS IHS) - Scheie variant (attenuated mucopolysaccharidosis I; also, MPS IS)
- Diagnosis of MPS I is confirmed by one of the following: - Deficiency or absence of fibroblast or leukocyte enzyme activity of alpha-L-iduronidase enzyme activity - Molecular genetic confirmation of mutations in the alpha-L-iduronidase gene
- Presence of clinical signs and symptoms of the disease (e.g., asymptomatic with affected older sibling, cardiac abnormalities, corneal clouding, dysostosis multiplex, hepatomegaly, restrictive lung disease, etc.)

Provider Actions and Prior Authorization Requirements

Prior Authorization

Initial Authorization Duration

Initial authorizations for all listed therapies are limited to no more than 12 months. Prior authorization is required to determine medical necessity under the drug-specific criteria.

Prior Authorization

Continuation/Reauthorization Requirements

For reauthorization, providers must document prior receipt of the specific therapy and evidence of positive clinical response (examples provided per drug) and confirm dosing is in accordance with FDA labeling; reauthorizations are limited to no more than 12 months.

Applicable Codes

Aldurazyme HCPCSHCPCSCovered

J1931

Injection, laronidase, 0.1 mg

Elaprase HCPCSHCPCSCovered

J1743

Injection, idursulfase, 1 mg

Elfabrio HCPCSHCPCSCovered

J2508

Injection, pegunigalsidase alfa-iwxj, 1 mg

Fabrazyme HCPCSHCPCSCovered

J0180

Injection, agalsidase beta, 1 mg

Kanuma HCPCSHCPCSCovered

J2840

Injection, sebelipase alfa, 1 mg

Lamzede HCPCSHCPCSCovered

J0217

Injection, velmanase alfa-tycv, 1 mg

Mepsevii HCPCSHCPCSCovered

J3397

Injection, vestronidase alfa-vjbk, 1 mg

Naglazyme HCPCSHCPCSCovered

J1458

Injection, galsulfase, 1 mg

Nulibry HCPCSHCPCSCovered

J1809

Injection, fosdenopterin, 0.1 mg

Revcovi HCPCSHCPCSCovered

J3590

Unclassified biologic

Vimizim HCPCSHCPCSCovered

J1322

Injection, elosulfase alfa, 1 mg

Xenpozyme HCPCSHCPCSCovered

J0218

Injection, olipudase alfa-rpcp, 1 mg

Aldurazyme ICD-10 Diagnosis CodesICD-10Covered

E76.01	Hurler's syndrome
E76.02	Hurler-Scheie syndrome
E76.03	Scheie's syndrome

Elaprase ICD-10 Diagnosis CodesICD-10Covered

E76.1

Mucopolysaccharidosis, type II

Elfabrio / Fabrazyme ICD-10 Diagnosis CodesICD-10Covered

E75.21

Fabry (-Anderson) disease

Kanuma ICD-10 Diagnosis CodesICD-10Covered

E75.5

Other lipid storage disorders

Lamzede ICD-10 Diagnosis CodesICD-10Covered

E77.1

Defects in glycoprotein degradation

Mepsevii / Naglazyme ICD-10 Diagnosis CodesICD-10Covered

E76.29

Other mucopolysaccharidoses (includes Sly syndrome / Maroteaux-Lamy syndrome)

Nulibry ICD-10 Diagnosis CodesICD-10Covered

E72.10	Disorders of sulfur-bearing amino-acid metabolism, unspecified
E72.19	Other disorders of sulfur-bearing amino-acid metabolism

Revcovi ICD-10 Diagnosis CodesICD-10Covered

D81.31

Severe combined immunodeficiency due to adenosine deaminase deficiency

Vimizim ICD-10 Diagnosis CodesICD-10Covered

E76.210

Morquio A mucopolysaccharidoses

Xenpozyme ICD-10 Diagnosis CodesICD-10Covered

E75.241	Niemann-Pick disease type B; ASMD type B & chronic visceral ASM deficiency
E75.244	Niemann-Pick disease type A/B; ASMD type A/B & chronic neurovisceral ASM deficiency

Removed HCPCS codesHCPCS

J0221	Lumizyme (alglucosidase alfa) - removed
J0219	Nexviazyme (avalglucosidase alfa-ngpt) - removed

Removed ICD-10 diagnosis codesICD-10

E74.02

Glycogen storage disease type II (Pompe disease) - removed association with Lumizyme/Nexviazyme

FDA-indicated therapies referenced in this partmixed

Aldurazyme	laronidase - indicated for Hurler and Hurler-Scheie MPS I forms (FDA labeling referenced)
Elaprase	idursulfase - indicated for Hunter syndrome (MPS II)
Elfabrio	pegunigalsidase alfa-iwxj - indicated for adults with Fabry disease
Fabrazyme	agalsidase beta - indicated for Fabry disease
Kanuma	sebelipase alfa - indicated for lysosomal acid lipase deficiency
Lamzede	velmanase alfa-tycv - indicated for non-CNS manifestations of alpha-mannosidosis
Mepsevii	vestronidase alfa-vjbk - indicated for MPS VII
Naglazyme	galsulfase - indicated for MPS VI
Nulibry	fosdenopterin - indicated to reduce risk of mortality in MoCD type A
Revcovi	elapegademase-lvlr - indicated for ADA-SCID

1–10 of 12

1/2

Clinical Evidence Summary

+38.1mAldurazyme 6MWT change vs placebo at 26 weeks

+37mElaprase 6MWT change (weekly) at 53 weeks

+22.5mVimizim MOR-004 6MWT improvement (weekly vs placebo)

DLco +20.9%Xenpozyme Trial 1 (adults): DLco % change at 52 weeks

Spl -39.4%Xenpozyme Trial 1 (adults): spleen volume change at 52 weeks

+92mNaglazyme 12MWT improvement vs placebo; urine GAG decline

ALT norm 31%Kanuma: ALT normalization 31% vs 7% with placebo

OS HR 0.18Nulibry: improved overall survival vs historical control (HR 0.18; 95% CI 0.04–0.72)

Background and Definitions

Provides mechanism of action and clinical rationale summaries for multiple enzyme-replacement and related therapies used in lysosomal and other enzyme deficiency disorders: examples include recombinant α-L-iduronidase (Aldurazyme) to catabolize dermatan/heparan sulfate, iduronate-2-sulfatase (Elaprase), α-galactosidase A products (Elfabrio/Fabrazyme), lysosomal acid lipase (Kanuma), alpha-mannosidase (Lamzede), beta-glucuronidase (Mepsevii), arylsulfatase B (Naglazyme), fosdenopterin for molybdenum cofactor restoration (Nulibry), recombinant ADA (Revcovi), elosulfase alfa (Vimizim), and olipudase alfa (Xenpozyme). Key trial evidence demonstrates improvements in functional endpoints (e.g., 6MWT, 12MWT, DLco, stair-climb tests), reductions in organ volumes or biomarkers (e.g., spleen volume, liver volume, urine GAG, plasma GL-3, ALT normalization), and survival benefit in selected indications.

FDA section informational: FDA approval information included for informational purposes only; FDA approval alone is not a basis for coverage under this policy.

Revision History

2026-03-01material_revisionLatest

Revised policy to remove Lumizyme (alglucosidase alfa) and Nexviazyme (avalglucosidase alfa-ngpt) from the list of applicable medical therapies; replaced prior internal coverage linkage for these products with requirement that coverage is contingent on the state's Medicaid clinical policy; removed coverage guidelines for Lumizyme and Nexviazyme; removed HCPCS codes J0221 and J0219 and ICD-10 code E74.02 associated with these products from the policy; updated Background, Clinical Evidence, FDA, and References sections to reflect current information.

Policy Summary

Payerunitedhealthcare

PolicyMedical Therapies for Enzyme Deficiencies (for Indiana Only)

Policy CodePolicy CSIND0052.16

Change TypeRemoved therapies; code/diagnosis removals; updated clinical sections

Effective DateMar 1, 2026

Next Review Date

Key ActionInitial authorizations for all listed therapies are limited to no more than 12 months; prior authorization is required to determine medical necessity under the drug-specific criteria.

SourceLink

On This Page

Dosing is in accordance with the United States Food and Drug Administration (FDA) approved labeling

Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with laronidase therapy; and
Patient has experienced a positive clinical response to laronidase therapy (e.g., improved endurance, improved functional capacity, reduced urine dermatan sulfate/heparan sulfate excretion, etc.)
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Elaprase (idursulfase) - Initial and Continuation Therapy Criteria

Elaprase (idursulfase) is medically necessary for the treatment of mucopolysaccharidosis II (MPS II, Hunter Syndrome) when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of MPS II confirmed by one of the following: - Deficiency in iduronate 2-sulfatase enzyme activity as measured in fibroblasts or leukocytes combined with normal enzyme activity level of another sulfatase - Molecular genetic testing for deletion or mutations in the iduronate 2-sulfatase gene
- Presence of clinical signs and symptoms of the disease (e.g., hepatosplenomegaly, skeletal deformities, dysostosis, neurocognitive decline, cardiovascular disorders, etc.)
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with idursulfase therapy; and
Patient has experienced a positive clinical response to idursulfase therapy (e.g., improved endurance, improved functional capacity, reduced spleen volume, reduced urine glycosaminoglycan excretion, etc.)
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Elfabrio (pegunigalsidase alfa-iwxj) - Initial and Continuation Therapy Criteria

Elfabrio (pegunigalsidase alfa-iwxj) is proven for the treatment of adults with confirmed Fabry disease. Elfabrio is medically necessary when the following additional criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of Fabry disease as confirmed by one of the following: - Absence or deficiency (< 5% of mean) of normal alpha-galactosidase A (α-Gal A) enzyme activity in leukocytes, dried blood spots, or serum analysis - Molecular genetic testing for deletion or mutations in the galactosidase alpha gene
- Presence of clinical signs and symptoms of the disease (e.g., acroparesthesias, angiokeratomas, whorls, anhidrosis/hypohidrosis, renal disease, exercise/heat/cold intolerance, etc.)
- Patient is not receiving Elfabrio in combination with another disease-modifying therapy used for the treatment of Fabry disease [e.g., Fabrazyme (agalsidase beta), Galafold (migalastat)]
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with pegunigalsidase alfa-iwxj therapy; and
Patient has experienced a positive clinical response to pegunigalsidase alfa-iwxj therapy (e.g., improved renal function, reduction in mean plasma GL-3 levels, decreased GL-3 inclusions, etc.)
Patient is not receiving Elfabrio in combination with another disease-modifying therapy used for the treatment of Fabry disease [e.g., Fabrazyme (agalsidase beta), Galafold (migalastat)]
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months

Fabrazyme (agalsidase beta) - InterQual Reference

Fabrazyme (agalsidase beta) is medically necessary for the treatment of Fabry disease. For medical necessity clinical coverage criteria for Fabrazyme, refer to the current release of the InterQual® guideline.

ALL of the following

Refer to the current release of the InterQual® guideline: CP: Specialty Rx NonOncology, Agalsidase beta (Fabrazyme).

Kanuma (sebelipase alfa) - Initial and Continuation Therapy Criteria

Kanuma (sebelipase alfa) is medically necessary for the treatment of Lysosomal acid lipase deficiency [LAL-D, Wolman disease (WD), cholesteryl ester disease (CESD)] when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of lysosomal acid lipase deficiency [LAL-D, Wolman disease (WD), cholesteryl ester disease (CESD)] as confirmed by one of the following: - Absence or deficiency lysosomal acid lipase activity by dried blood spot test - Molecular genetic testing for deletion or mutations in the lipase A, lysosomal acid type (LIPA) gene
- Presence of clinical signs and symptoms of the disease (e.g., abdominal distention, hepatosplenomegaly, liver fibrosis, ascites, etc.)
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with sebelipase alfa therapy; and
Patient has experienced a positive clinical response to sebelipase alfa therapy [e.g., improved disease symptoms, improvement of laboratory values (LFTs, cholesterol, triglycerides), etc.]
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Lamzede (velmanase alfa-tycv) - Initial and Continuation Therapy Criteria

Lamzede (velmanase alfa-tycv) is proven and medically necessary for the treatment of alpha-mannosidosis when the following additional criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of alpha-mannosidosis confirmed by one of the following: - Absence or deficiency (< 10% of the lab specific normal mean) of alpha-mannosidase enzyme activity - Molecular genetic testing for mutations in the MAN2B1 gene
- Presence of clinical signs and symptoms of the disease (e.g., hepatosplenomegaly, skeletal abnormalities, ataxia, intellectual disability, hearing loss)
- Lamzede (velmanase alfa-tycv) is not being used to treat central nervous system (CNS) manifestations of alphamannosidosis
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with Lamzede (velmanase alfa-tycv) therapy; and
Patient has experienced a positive clinical response to Lamzede (velmanase alfa-tycv) therapy (e.g., improved motor function, improved pulmonary function)
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Mepsevii (vestronidase alfa-vjbk) - Initial and Continuation Therapy Criteria

Mepsevii (vestronidase alfa-vjbk) is proven and medically necessary for the treatment of mucopolysaccharidosis VII (MPS VII, Sly syndrome) when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of mucopolysaccharidosis VII confirmed by one of the following: - Absence or deficiency of fibroblast or leukocyte enzyme activity of beta glucuronidase - Molecular genetic confirmation of mutations in the GUSB gene
- Presence of clinical signs and symptoms of the disease (e.g., enlarged liver and spleen, joint limitations, airway obstruction or pulmonary problems, limitation of mobility while still ambulatory, etc.)
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with vestronidase alfa-vjbk therapy; and
Patient has experienced a positive clinical response to vestronidase alfa-vjbk therapy (e.g., improved endurance, improved functional capacity, improved pulmonary function, etc.)
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Naglazyme (galsulfase) - Initial and Continuation Therapy Criteria

Naglazyme (galsulfase) is medically necessary for the treatment of mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of mucopolysaccharidosis VI confirmed by one of the following: - Absence or deficiency of fibroblast or leukocyte enzyme activity of N-acetylgalactosamine 4-sulfatase (arylsulfatase) - Molecular genetic confirmation of mutations in the ASB gene (5q13-q14)
- Presence of clinical signs and symptoms of the disease (e.g., kyphoscoliosis, genu valgum, pectus carinatum, gait disturbance, growth deficiency, etc.)
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with galsulfase therapy; and
Patient has experienced a positive clinical response to galsulfase therapy (e.g., improved endurance, improved functional capacity, reduced urine dermatan sulfate excretion, etc.)
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Nulibry (fosdenopterin) - Initial and Continuation Therapy Criteria

Nulibry (fosdenopterin) is medically necessary for the treatment of molybdenum cofactor deficiency (MoCD) type A when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of molybdenum cofactor deficiency (MoCD) type A confirmed by one of the following: - Absence or deficiency of sulfite oxidase enzyme activity in fibroblasts - Molecular genetic testing for mutations in the MOCS1 gene
- Presence of clinical signs and symptoms of the disease (e.g., seizures, exaggerated startle, feeding difficulties, hypotonia, developmental delay) and neonatal-onset specifics as applicable
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with fosdenopterin therapy; and
Patient has experienced a positive clinical response to fosdenopterin therapy
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Revcovi (elapegademase-lvlr) - Initial and Continuation Therapy Criteria

Revcovi (elapegademase-lvlr) is medically necessary for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID) when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Patient is diagnosed with ADA-SCID and is not a candidate for hematopoietic cell transplantation (HCT) or HCT is not immediately available; and
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with elapegademase-lvlr therapy; and
Patient has experienced a positive clinical response to elapegademase-lvlr therapy
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Vimizim (elosulfase alfa) - Initial and Continuation Therapy Criteria

Vimizim (elosulfase alfa) is medically necessary for the treatment of mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of mucopolysaccharidosis IVA confirmed by one of the following: - Absence or deficiency of fibroblast or leukocyte enzyme activity of N-acetylgalactosamine-6-sulfatase (GALNS) - Molecular genetic confirmation of mutations in the GALNS gene
- Presence of clinical signs and symptoms of the disease (e.g., skeletal abnormalities, short stature, airway compromise, corneal clouding)
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with elosulfase alfa therapy; and
Patient has experienced a positive clinical response to elosulfase alfa therapy
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Xenpozyme (olipudase alfa-rpcp) - Initial and Continuation Therapy Criteria

Xenpozyme (olipudase alfa-rpcp) is proven and medically necessary for the treatment of non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) when the following criteria are met:

ALL of the following

For initial therapy, all of the following:
ALL of the following
- Diagnosis of acid sphingomyelinase deficiency (ASMD) confirmed by one of the following: - Deficiency or marked reduction of acid sphingomyelinase enzyme activity - Molecular genetic testing consistent with ASMD
- Xenpozyme (olipudase alfa-rpcp) is not being used to treat CNS manifestations of ASMD
- Presence of clinical signs and symptoms of non-CNS ASMD (e.g., hepatosplenomegaly, pulmonary disease, dyslipidemia)
- Dosing is in accordance with the U.S. FDA approved labeling
- Initial authorization will be for no more than 12 months<= 12 months

Continuation of Therapy

For continuation of therapy, all of the following:
Patient has previously received treatment with olipudase alfa-rpcp therapy; and
Patient has experienced a positive clinical response to olipudase alfa-rpcp therapy
Dosing is in accordance with the U.S. FDA approved labeling
Reauthorization will be for no more than 12 months<= 12 months

Documentation Required

Diagnostic Confirmation Required

Providers must document confirmation of diagnosis by biochemical enzyme testing or molecular genetic testing as specified for each therapy, and document the presence of clinical signs or symptoms consistent with the disorder.

Aldurazyme: deficiency/absence of fibroblast or leukocyte alpha-L-iduronidase activity or molecular genetic confirmation of alpha-L-iduronidase gene mutations (see Aldurazyme criteria).
Elaprase: deficiency in iduronate 2-sulfatase enzyme activity in fibroblasts or leukocytes or molecular genetic testing for iduronate 2-sulfatase gene mutations (see Elaprase criteria).
Elfabrio/Fabrazyme (Fabry): absence or deficiency (<5% of mean) of alpha-galactosidase A enzyme activity or molecular genetic testing for galactosidase alpha gene mutations (see Elfabrio/Fabrazyme criteria).
Kanuma: absence or deficiency of lysosomal acid lipase activity by dried blood spot test or molecular genetic testing for LIPA gene mutations (see Kanuma criteria).
Lamzede: absence or deficiency (<10% lab-specific mean) of alpha-mannosidase activity or molecular genetic testing for MAN2B1 mutations (see Lamzede criteria).
Mepsevii: absence or deficiency of beta-glucuronidase activity or molecular genetic confirmation of GUSB mutations (see Mepsevii criteria).
Naglazyme: absence or deficiency of N-acetylgalactosamine 4-sulfatase activity or molecular genetic confirmation of ASB gene mutations (see Naglazyme criteria).
Nulibry: absence or deficiency of sulfite oxidase activity in fibroblasts or molecular genetic testing for MOCS1 mutations (see Nulibry criteria).
Revcovi: deficiency/absence of ADA in appropriate specimens or molecular genetic confirmation of ADA1 mutations or supporting laboratory findings (see Revcovi criteria).
Vimizim: absence or deficiency of GALNS enzyme activity or molecular genetic testing for GALNS mutations (see Vimizim criteria).
Xenpozyme: absence or deficiency of acid sphingomyelinase activity or molecular genetic testing for SMPD1 mutations (see Xenpozyme criteria).

Documentation Required

Therapy Combination Exclusion (Elfabrio)

For Elfabrio, document that the patient is not receiving Elfabrio concurrently with another disease-modifying therapy for Fabry disease (for example, Fabrazyme or Galafold).

Documentation Required

CNS Use Exclusion (Lamzede, Xenpozyme)

For Lamzede and Xenpozyme, document that these therapies are not being used to treat central nervous system (CNS) manifestations when applicable (they are indicated for non‑CNS manifestations only).

Documentation Required

Use of third-party tools

UnitedHealthcare may use third-party tools, such as InterQual, to assist in administering health benefits; providers should be aware that such criteria may be applied in medical necessity determinations.

Prior Authorization

State Medicaid clinical policy may govern coverage

Coverage for Lumizyme (alglucosidase alfa) and Nexviazyme (avalglucosidase alfa-ngpt) is contingent on the state's Medicaid clinical policy rather than the Drug-Specific Criteria in this policy; providers should follow the state Medicaid clinical policy for coverage determinations.

J0221
J0219

Billing Rule

Removed codes must not be billed under this policy

HCPCS codes J0221 and J0219 and ICD-10 code E74.02 were removed from this policy as of 03/01/2026 and must not be billed under this policy; providers should follow state-specific Medicaid criteria for coverage decisions for those products.

J0221
J0219
E74.02

Documentation Required

Reference federal/state/contractual plan terms

Reference federal, state, or contractual plan terms for benefit coverage, as those requirements may differ from the standard UnitedHealthcare policy; in the event of conflict, federal/state/contractual requirements govern.

Enzyme-replacement and related therapies provide exogenous or recombinant forms of deficient lysosomal enzymes (or precursor cofactors) that are internalized into cells and targeted to lysosomes to increase catabolism of accumulated substrates; the Background section summarizes mechanism and rationale for multiple products. Part 2 of the policy includes updated clinical evidence summaries across therapies. FDA labeling is provided for informational purposes only and is not a basis for coverage. Selected evidence items referenced include trial endpoints such as the six-minute walk test (6MWT), diffusion capacity (DLco), spleen volume, alanine aminotransferase (ALT) normalization, and survival hazard ratios (HR).