CurrentUnitedHealthcarePolicy CSOH2026D0052.E

Medical Therapies Enzyme Deficiencies Oh Cs

State-specific UnitedHealthcare medical benefit drug policy for multiple enzyme-replacement and related therapies for inherited enzyme deficiencies in Ohio; defines drug-specific initial and continuation medical necessity criteria, required diagnostic confirmation, clinical signs/symptoms, dosing per FDA labeling, and authorization durations (typically ≤12 months).

Policy Summary

PayerUnitedHealthcare

PolicyMedical Therapies Enzyme Deficiencies Oh Cs

Policy CodePolicy CSOH2026D0052.E

Change TypeHCPCS code updates (J1809 added; C9399/J3490/J3590 removed)

Effective DateJan 1, 2026

Next Review Date

Key ActionInitial and continuation authorizations require documentation of diagnostic confirmation, presence of clinical signs/symptoms, dosing per FDA labeling, and demonstration of positive clinical response for reauthorization (authorizations limited to ≤12 months).

SourceLink

POLICY UPDATE CHANGES

HCPCS code J1809 added for Nulibry.

HCPCS codes C9399, J3490, and J3590 removed (previously used for Nulibry).

Previous policy version CSOH2025D0052.D archived.

15Drugs listed

≤12 monthsTypical initial/reauthorization duration

OhioPolicy scope

1Policy history revision entries (01/01/2026)

Coverage Summary

This Ohio-specific UnitedHealthcare medical benefit drug policy (effective 2026-01-01) covers multiple enzyme replacement and related therapies for inherited enzyme deficiencies. Coverage is conditional: each drug has product-specific diagnostic confirmation, required clinical signs/symptoms, dosing per FDA approved labeling, and prior authorization. Initial authorizations and reauthorizations are typically limited to no more than 12 months per the drug-specific criteria.

The policy scope applies only to the state of Ohio and directs providers to follow Ohio Administrative Code and applicable federal/state/contractual requirements when they differ from this standard policy.

Policy-level key values

policy_numberCSOH2026D0052.E

effective_dateJanuary 1, 2026

state_scopeOhio (state-specific medical benefit drug policy)

coverage_stancecovered_with_criteria

typical_initial_or_reauthorization_durationInitial and reauthorization periods typically ≤ 12 months

Initial Therapy Criteria (by product)

Elaprase (idursulfase) - MPS II

For initial therapy, all of the following:

ALL of the following

Diagnosis of Mucopolysaccharidosis II (MPS II, Hunter syndrome) confirmed by one of the following: deficiency in iduronate 2-sulfatase enzyme activity measured in fibroblasts or leukocytes combined with normal enzyme activity level of another sulfatase; or molecular genetic testing confirming deletion or pathogenic mutation(s) in the iduronate 2-sulfatase (IDS) gene.
Presence of clinical signs and symptoms consistent with MPS II (e.g., hepatosplenomegaly, skeletal deformities/dysostosis multiplex, respiratory disease, cardiac disease, neurocognitive decline for neuronopathic forms).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for idursulfase (Elaprase).
Initial authorization will be for no more than 12 months.

Continuation Therapy Criteria (by product)

Aldurazyme (laronidase) - Continuation of therapy

Continuation of therapy

ALL of the following

Patient has previously received laronidase therapy
Patient has experienced a positive clinical response to laronidase (e.g., improved endurance, improved functional capacity, reduced urine dermatan sulfate/heparan sulfate excretion, etc.)
Dosing is in accordance with FDA approved labeling
Reauthorization will be for no more than 12 months

Limitations / Exclusions

Combination use exclusions: the policy generally disallows combination use of more than one disease-modifying enzyme therapy for the same disorder; examples include: Elfabrio must not be used in combination with another disease-modifying Fabry therapy (e.g., Fabrazyme, migalastat), and Lumizyme and Nexviazyme must not be used in combination with other Pompe ERTs (e.g., Lumizyme, Nexviazyme, Pombiliti).

Pombiliti is allowed only when prescribed in combination with oral Opfolda (miglustat) and requires that the patient is not improving on their current ERT and that the current ERT will be stopped; Pombiliti must not be given concurrently with other disease-modifying Pompe enzyme therapies (e.g., Lumizyme, Nexviazyme).

Policy also instructs providers to use the updated HCPCS code J1809 for Nulibry and not to use prior codes (C9399, J3490, J3590) per the 01/01/2026 changes.

Applicable Codes

Aldurazyme HCPCSHCPCSCovered

J1931

Injection, laronidase, 0.1 mg

Aldurazyme Diagnosis CodesICD-10Covered

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

Elaprase HCPCSHCPCSCovered

J1743

Injection, idursulfase, 1 mg

Elaprase Diagnosis CodesICD-10Covered

E76.1

Mucopolysaccharidosis, type II

Elfabrio HCPCSHCPCSCovered

J2508

Injection, pegunigalsidase alfa-iwxj, 1 mg

Elfabrio / Fabry DiagnosisICD-10Covered

E75.21

Fabry (-Anderson) disease

Fabrazyme HCPCSHCPCSCovered

J0180

Injection, agalsidase beta, 1 mg

Kanuma HCPCS & DiagnosismixedCovered

J???	Injection, sebelipase alfa, 1 mg (code text in document incomplete)
E75.5	Other lipid storage disorders

Lamzede HCPCS & DiagnosismixedCovered

J0217	Injection, velmanase alfa-tycv, 1 mg
E77.1	Defects in glycoprotein degradation

Lumizyme HCPCS & DiagnosismixedCovered

J????	Injection, alglucosidase alfa (Lumizyme), 10 mg (HCPCS code not clearly specified in document)
E74.02	Pompe disease

Mepsevii HCPCS & DiagnosismixedCovered

J3397	Injection, vestronidase alfa-vjbk, 1 mg
E76.29	Other mucopolysaccharidoses (includes Sly syndrome)

Naglazyme HCPCSHCPCSCovered

J????

Injection, galsulfase, 1 mg (exact HCPCS code not clearly shown)

Nexviazyme / Nulibry / Other HCPCS (mixed entries)mixedCovered

J1809

Listed in document (context shows multiple entries; document text is fragmented)

Pombiliti HCPCSHCPCSCovered

J1203

Injection, cipaglucosidase alfa-atga (document lists J1203)

Pombiliti DiagnosisICD-10Covered

E74.02

Pompe disease

Revcovi HCPCSHCPCSCovered

J3590

Reimbursable code listed for Revcovi in document

Revcovi DiagnosisICD-10Covered

D81.31

Severe combined immunodeficiency due to adenosine deaminase deficiency

Vimizim HCPCS & DiagnosismixedCovered

J1322	Injection, elosulfase alfa, 1 mg
E76.210	Mucopolysaccharidosis type IVA (Morquio A)

Xenpozyme HCPCS & DiagnosismixedCovered

J0218	Injection, olipudase alfa-rpcp, 1 mg
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

Updated HCPCS codes (Policy History)HCPCSCovered

J1809

Added HCPCS code for Nulibry (01/01/2026 Summary of Changes)

Removed HCPCS codes (Policy History)HCPCSNot Covered

C9399	Removed (01/01/2026 Summary of Changes)
J3490	Removed (01/01/2026 Summary of Changes)
J3590	Removed (01/01/2026 Summary of Changes)

Provider Actions & Authorization Requirements

Prior Authorization

Prior authorization required

Initial and continuation authorizations require documentation of diagnostic confirmation, presence of clinical signs/symptoms, dosing per FDA labeling, and demonstration of positive clinical response for reauthorization. Initial and reauthorization periods are limited to no more than 12 months.

Documentation Required

Diagnostic documentation

Provider must supply laboratory confirmation (enzyme assay or molecular genetic testing as specified per drug) and documentation of clinical signs/symptoms consistent with the indicated disorder.

Clinical Evidence

0.18Nulibry overall survival HR vs natural history

+25mLumizyme 6MWT mean change (vs placebo)

+30mNexviazyme 6MWT difference vs alglucosidase alfa

+20.9%Xenpozyme DLco mean percent change vs placebo

Aldurazyme RCT: Wraith et al. — randomized, double-blind, placebo-controlled study (n=45) showing improved % predicted FVC, increased 6MWT distance, reduced hepatomegaly and decreased urinary GAGs over 26 weeks.

Elaprase RCT: Muenzer et al. — randomized, double-blind, placebo-controlled trial (n≈96) demonstrating significant improvement in a composite endpoint (%FVC and 6MWT), increased 6MWT distance, and reduced liver volume and urine GAGs at 53 weeks.

Elfabrio trials: Open-label dose-ranging and a randomized active-controlled study in ERT-experienced adults showed renal and eGFR outcomes with infusion-associated reactions reported; in the active-controlled study eGFR slopes were similar to agalsidase beta.

Fabrazyme trial clinical events: a randomized trial in advanced Fabry disease found a hazard ratio for time to first clinical event of 0.47 (95% CI 0.21–1.03; p=0.06), with protocol-adherent analysis HR 0.39 (0.16–0.93; p=0.034).

Background

These therapies are recombinant or exogenous enzyme-based treatments intended to replace deficient lysosomal enzymes. Products are produced by recombinant DNA technology (commonly in CHO or human cell lines or E. coli platforms) and are designed for cellular uptake—typically via mannose-6-phosphate or other glycan receptor–mediated internalization—targeting lysosomes to catabolize accumulated substrates specific to each disorder.

Key definitions: FDA approved labeling — product-specific dosing and administration per U.S. FDA prescribing information; ERT — enzyme replacement therapy; other terms defined in the policy include eGFR and 6MWT as standard clinical measures used in trials and reauthorization assessments.

Thresholds (from policy)

Elfabrio alpha-Gal A enzyme activity< 5% of mean

Lamzede alpha-mannosidase activity< 10% of the lab specific normal mean

Lumizyme infantile GAA activity< 1% of the lab specific normal mean

Lumizyme late-onset GAA activity< 40% of the lab specific normal mean

Revision History

2026-01-01addedLatest

HCPCS code J1809 added for Nulibry.

2026-01-01removedLatest

HCPCS codes C9399, J3490, and J3590 removed (previously used for Nulibry).

2026-01-01revisedLatest

Policy Summary

PayerUnitedHealthcare

PolicyMedical Therapies Enzyme Deficiencies Oh Cs

Policy CodePolicy CSOH2026D0052.E

Change TypeHCPCS code updates (J1809 added; C9399/J3490/J3590 removed)

Effective DateJan 1, 2026

Next Review Date

SourceLink

On This Page

Elfabrio (pegunigalsidase alfa-iwxj) - Fabry disease (adults)

For initial therapy, all of the following:

ALL of the following

Diagnosis of Fabry disease confirmed by one of the following: absence or profound deficiency (<5% of mean) of alpha-galactosidase A (α-Gal A) enzyme activity in leukocytes, dried blood spot, or serum; or molecular genetic testing demonstrating a pathogenic variant in the GLA gene.
Patient is an adult (Elfabrio is proven for treatment in adults).
Presence of clinical signs or symptoms of Fabry disease (e.g., acroparesthesias, angiokeratomas, hypohidrosis/anhidrosis, progressive renal impairment, cardiomyopathy, gastrointestinal symptoms, cerebrovascular disease).
Patient is not receiving Elfabrio in combination with another disease-modifying therapy for Fabry disease (e.g., agalsidase beta [Fabrazyme], migalastat [Galafold]).
Dosing is in accordance with the United States Food and Drug Administration approved labeling for pegunigalsidase alfa (Elfabrio).
Initial authorization will be for no more than 12 months.

Fabrazyme (agalsidase beta) - Fabry disease

Refer to the current InterQual guideline for initial therapy criteria.

ALL of the following

Fabry disease diagnosis per clinical and laboratory confirmation as specified in InterQual CP: Specialty Rx NonOncology Agalsidase beta (Fabrazyme).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for agalsidase beta (Fabrazyme).
Initial authorization length and supporting documentation per InterQual guidance.

Kanuma (sebelipase alfa) - Lysosomal acid lipase deficiency (LAL-D, Wolman disease, CESD)

For initial therapy, all of the following:

ALL of the following

Diagnosis of lysosomal acid lipase deficiency (LAL-D), including Wolman disease (infantile) or cholesteryl ester storage disease (CESD), confirmed by one of the following: absent or deficient LAL enzyme activity by dried blood spot or leukocyte/fibroblast testing; or molecular genetic testing showing pathogenic variants in the LIPA gene.
Presence of clinical signs and symptoms consistent with LAL-D (e.g., hepatomegaly, splenomegaly, elevated transaminases, liver fibrosis, failure to thrive, lipid abnormalities, gastrointestinal symptoms).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for sebelipase alfa (Kanuma).
Initial authorization will be for no more than 12 months.

Lamzede (velmanase alfa-tycv) - alpha-mannosidosis

For initial therapy, all of the following:

ALL of the following

Diagnosis of alpha-mannosidosis confirmed by one of the following: absent or deficient alpha-mannosidase enzyme activity (<10% of lab-specific normal mean); or molecular genetic testing showing pathogenic variant(s) in the MAN2B1 gene.
Presence of clinical signs and symptoms of alpha-mannosidosis (e.g., developmental delay/intellectual disability, hearing loss, recurrent infections, skeletal abnormalities, ataxia, hepatosplenomegaly).
Lamzede is not being used specifically to treat central nervous system (CNS) manifestations (CNS disease benefit not established).
Dosing is in accordance with the United States Food and Drug Administration approved labeling for velmanase alfa (Lamzede).
Initial authorization will be for no more than 12 months.

Lumizyme (alglucosidase alfa) - Pompe disease

For initial therapy, one of the following (infantile-onset or late-onset criteria):

ANY of the following

Infantile-onset Pompe disease
- Diagnosis of infantile-onset Pompe disease confirmed by one of the following: absent or deficient acid alpha-glucosidase (GAA) activity (<1% of lab-specific normal mean) in skin fibroblasts; or molecular genetic testing showing pathogenic variants in the GAA gene.
- Presence of clinical signs and symptoms of infantile-onset Pompe disease (e.g., cardiomyopathy/cardiac hypertrophy, hypotonia, respiratory insufficiency, feeding difficulties).
- Patient is not receiving Lumizyme in combination with another disease-modifying enzyme therapy for Pompe disease (e.g., avalglucosidase alfa [Nexviazyme], cipaglucosidase alfa [Pombiliti]).
- Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for alglucosidase alfa (Lumizyme).
- Initial authorization will be for no more than 12 months.
Late-onset (non-infantile) Pompe disease
- Diagnosis of late-onset Pompe disease confirmed by one of the following: absent or deficient acid alpha-glucosidase (GAA) activity (<40% of lab-specific normal mean) in lymphocytes, fibroblasts, or muscle; or molecular genetic testing showing pathogenic variants in the GAA gene.
- Presence of clinical signs and symptoms of late-onset Pompe disease (e.g., progressive limb-girdle weakness, respiratory muscle weakness, exertional dyspnea).
- Patient is not receiving Lumizyme in combination with another disease-modifying enzyme therapy for Pompe disease (e.g., avalglucosidase alfa [Nexviazyme], cipaglucosidase alfa [Pombiliti]).
- Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for alglucosidase alfa (Lumizyme).
- Initial authorization will be for no more than 12 months.

Mepsevii (vestronidase alfa-vjbk) - MPS VII (Sly syndrome)

For initial therapy, all of the following:

ALL of the following

Diagnosis of mucopolysaccharidosis VII (MPS VII, Sly syndrome) confirmed by one of the following: deficient beta-glucuronidase enzyme activity in leukocytes or fibroblasts; or molecular genetic testing demonstrating pathogenic variant(s) in the GUSB gene.
Presence of clinical signs and symptoms of MPS VII (e.g., short stature, hepatosplenomegaly, skeletal abnormalities, pulmonary compromise, developmental delay).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for vestronidase alfa (Mepsevii).
Initial authorization will be for no more than 12 months.

Naglazyme (galsulfase) - MPS VI

For initial therapy, all of the following:

ALL of the following

Diagnosis of mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) confirmed by one of the following: deficiency of arylsulfatase B (ARSB) enzyme activity in leukocytes or fibroblasts; or molecular genetic testing demonstrating pathogenic variant(s) in the ARSB gene.
Presence of clinical signs and symptoms of MPS VI (e.g., short stature, skeletal dysplasia, joint stiffness, corneal clouding, cardiac disease, hepatosplenomegaly).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for galsulfase (Naglazyme).
Initial authorization will be for no more than 12 months.

Nexviazyme (avalglucosidase alfa-ngpt) - late-onset Pompe disease

For initial therapy, all of the following:

ALL of the following

Diagnosis of late-onset Pompe disease confirmed by one of the following: absent or deficient acid alpha-glucosidase (GAA) activity (<40% of lab-specific normal mean) in lymphocytes, fibroblasts, or muscle; or molecular genetic testing showing pathogenic variants in the GAA gene.
Presence of clinical signs and symptoms of late-onset Pompe disease (e.g., progressive limb-girdle weakness, respiratory muscle weakness, exertional dyspnea).
Patient is not receiving Nexviazyme in combination with another disease-modifying enzyme therapy for Pompe disease (e.g., alglucosidase alfa [Lumizyme], cipaglucosidase alfa [Pombiliti]).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for avalglucosidase alfa (Nexviazyme).
Initial authorization will be for no more than 12 months.

Pombiliti (cipaglucosidase alfa-atga) - late-onset Pompe disease

For initial therapy, all of the following:

ALL of the following

Diagnosis of late-onset Pompe disease confirmed by one of the following: absent or deficient acid alpha-glucosidase (GAA) activity (<40% of lab-specific normal mean) in lymphocytes, fibroblasts, or muscle; or molecular genetic testing showing pathogenic variants in the GAA gene.
Presence of clinical signs and symptoms of late-onset Pompe disease (e.g., progressive limb-girdle weakness, respiratory muscle weakness, exertional dyspnea).
Patient is not receiving Pombiliti in combination with another disease-modifying enzyme therapy for Pompe disease (e.g., alglucosidase alfa [Lumizyme], avalglucosidase alfa [Nexviazyme]).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for cipaglucosidase alfa (Pombiliti).
Initial authorization will be for no more than 12 months.

Revcovi (elapegademase-lvlr) - ADA-SCID

For initial therapy, all of the following:

ALL of the following

Diagnosis of adenosine deaminase severe combined immunodeficiency (ADA-SCID) confirmed by one of the following: absent or markedly reduced ADA enzyme activity in red blood cells/leukocytes; or molecular genetic testing showing pathogenic variant(s) in the ADA gene.
Presence of clinical signs and symptoms consistent with ADA-SCID (e.g., severe recurrent infections, failure to thrive, profound lymphopenia, absence of thymic shadow).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for elapegademase-lvlr (Revcovi).
Initial authorization will be for no more than 12 months.

Vimizim (elosulfase alfa) - MPS IVA (Morquio A)

For initial therapy, all of the following:

ALL of the following

Diagnosis of mucopolysaccharidosis IVA (MPS IVA, Morquio A) confirmed by one of the following: deficient N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity in leukocytes or fibroblasts; or molecular genetic testing demonstrating pathogenic variant(s) in the GALNS gene.
Presence of clinical signs and symptoms of MPS IVA (e.g., skeletal dysplasia, short stature, restrictive pulmonary disease, odontoid hypoplasia, corneal clouding may be absent).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for elosulfase alfa (Vimizim).
Initial authorization will be for no more than 12 months.

Xenpozyme (olipudase alfa-rpcp) - ASMD

For initial therapy, all of the following:

ALL of the following

Diagnosis of acid sphingomyelinase deficiency (ASMD; formerly Niemann–Pick disease types A/B) confirmed by one of the following: deficient acid sphingomyelinase enzyme activity in leukocytes or fibroblasts; or molecular genetic testing demonstrating pathogenic variant(s) in the SMPD1 gene.
Presence of clinical signs and symptoms of ASMD (e.g., hepatosplenomegaly, pulmonary disease, thrombocytopenia, growth failure, interstitial lung disease).
Dosing is in accordance with the U.S. Food and Drug Administration (FDA) approved labeling for olipudase alfa (Xenpozyme).
Initial authorization will be for no more than 12 months.

Documentation Required

Continuation response documentation

For continuation, provider must document prior receipt of the specific therapy and objective or clinical evidence of a positive response (examples provided per drug). Reauthorization periods are limited to no more than 12 months.

Billing Rule

Dosing and combination-use billing rules

Dosing must be in accordance with the FDA approved labeling for each product; combination use with another disease-modifying enzyme therapy for the same disease is generally disallowed unless specifically permitted by the drug-specific criteria.

Prior Authorization

Pombiliti specific prerequisites

Provider attestation required that the patient is not improving on current ERT and that the current ERT will be stopped; patient must weigh ≥ 40 kg and Pombiliti must be prescribed in combination with oral Opfolda (miglustat).

Codes: J1203

Billing Rule

Use updated HCPCS code for Nulibry

As of 01/01/2026, report Nulibry using HCPCS code J1809. Do not use previously used codes C9399, J3490, or J3590 for Nulibry.

New code: J1809
Removed codes: C9399, J3490, J3590
Effective date: 01/01/2026

Documentation Required

Reference federal/state/contract terms

When deciding coverage, reference federal, state (Ohio Administrative Code), or contractual requirements which may differ from this standard benefit policy; in the event of conflict, those requirements govern.

Lamzede (alpha-mannosidase): Phase 3 trial showed large reduction in serum oligosaccharide at 52 weeks (adjusted mean difference -70.5%; p<0.001) with mixed functional endpoint results.

Lumizyme (alglucosidase alfa) LOPD: randomized trial demonstrated mean 6MWT increase of 25.1 m versus -3.0 m for placebo (treatment effect 28.1 m; p=0.03) and FVC treatment effect 3.4 percentage points (p=0.006).

Nexviazyme vs alglucosidase alfa: randomized trial in late-onset Pompe disease reported FVC LS mean change 2.9% vs 0.5% (treatment difference 2.4%, 95% CI -0.1, 5) and 6MWT difference 30 m (95% CI 1.3, 58.7; p=0.04).

Nulibry (fosdenopterin): pooled studies versus natural history showed improved overall survival versus untreated cohort (HR 0.18; 95% CI 0.04, 0.72) and sustained urine SSC reduction to 48 months.

Pombiliti (cipaglucosidase alfa + miglustat): randomized active-controlled trial showed sitting FVC change difference 2.3% (95% CI 0.02, 4.62) and 6MWD difference 14 m (95% CI -1, 28).

Revcovi (elapegademase-lvlr) ADA‑SCID: studies demonstrated patients achieved target dAXP ≤0.02 mmol/L and trough ADA activity ≥15 mmol/hr/L, maintaining metabolic detoxification.

Vimizim (elosulfase alfa) MOR‑004: phase 3 trial found weekly regimen improved 6MWT by 22.5 m (95% CI 4.0, 40.9; p=0.017); every‑other‑week regimen was not different from placebo; high immunogenicity observed without correlation to efficacy.

Xenpozyme (olipudase alfa): randomized trial reported DLco percent change +20.9% vs placebo (p=0.0003); spleen volume -39.4% (p<0.0001); liver volume -24.7% (p<0.0001); platelet count +15.6% (p=0.028).

Nexviazyme/Pombiliti GAA activity< 40% of the lab specific normal mean

Aldurazyme authorization durationInitial/reauthorization ≤ 12 months

Previous policy version CSOH2025D0052.D archived.