CurrentCignaPolicy N/A

Enzyme Replacement Therapy - Naglazyme

This policy governs prior authorization, coverage criteria, dosing limits, and coding for Naglazyme (galsulfase) infusion for treatment of Mucopolysaccharidosis type VI (MPS VI) for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyEnzyme Replacement Therapy - Naglazyme

Policy CodePolicy N/A

Change TypeTitle and dosing language updated

Effective DateAug 1, 2024

Next Review DateMay 7, 2026

Key ActionPrior authorization is required; approve for 1 year if diagnostic confirmation and specialist involvement are documented.

SourceLink

POLICY UPDATE CHANGES

Updated coverage policy title from Galsulfase to Enzyme Replacement Therapy - Naglazyme and added dosing for Mucopolysaccharidosis Type VI.

1 yearinitial approval duration

≤1 mg/kgmax dose

weeklyfrequency

J1458covered code

Coverage Criteria for Naglazyme (galsulfase)

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.

Mucopolysaccharidosis Type VI (FDA-Approved Indication)

Approve for 1 year if the patient meets BOTH of the following (A and B):

FDA-Approved Indication Criteria

A) Diagnosis established by ONE of
- i) Laboratory demonstration of deficient N-acetylgalactosamine 4-sulfatase (arylsulfatase B) activity in leukocytes or fibroblasts.
- ii) Molecular genetic test demonstrating biallelic pathogenic or likely pathogenic ARSB (arylsulfatase B) gene variants.
B) Naglazyme is prescribed by or in consultation with a geneticist, endocrinologist, a metabolic disorder sub-specialist, or a physician who specializes in the treatment of lysosomal storage disorders.

Diagnostic confirmation of MPS VI to establish eligibility for Naglazyme

Coverage requires demonstration of either enzymatic deficiency or confirmatory molecular genetic testing:

Diagnostic confirmation (one required)

Enzyme assay demonstrating deficient N-acetylgalactosamine 4-sulfatase (arylsulfatase B) activity in leukocytes or fibroblasts (definitive diagnostic criterion).
Molecular genetic testing demonstrating biallelic pathogenic or likely pathogenic variants in the ARSB gene.

Provider Actions and Requirements

Prior Authorization

Prior authorization required; approve for 1 year if criteria met

Prior authorization is required for benefit coverage of Naglazyme; when criteria are met, approve for 1 year. Approval requires diagnostic confirmation and that Naglazyme be prescribed by or in consultation with an appropriate specialist.

Approve duration = 1 year when both diagnostic criteria and specialist involvement are documented.

Step Therapy

Dose exceptions reviewed case-by-case by clinician

Requests for doses outside the established dosing documented in this policy will be reviewed on a case-by-case basis by a clinician (e.g., Medical Director or Pharmacist).

Established dosing limit: each dose must not exceed 1 mg/kg IV no more frequently than once weekly.

Documentation Required

Required clinical documentation for approval

Approval requires documentation of diagnosis established by either an enzyme assay demonstrating deficient N‑acetylgalactosamine 4‑sulfatase (arylsulfatase B) activity in leukocytes or fibroblasts, or a molecular genetic test demonstrating biallelic pathogenic or likely pathogenic ARSB variants, and that Naglazyme is prescribed by or in consultation with an appropriate specialist.

Enzyme assay demonstrating deficient ARSB activity in leukocytes or fibroblasts; OR
Molecular genetic test showing biallelic pathogenic/likely pathogenic ARSB variants; AND
Prescription by or consultation with a geneticist, endocrinologist, metabolic disorder sub‑specialist, or physician who specializes in lysosomal storage disorders.

Denial Risk

Denial risk if not billed with covered diagnosis/procedure codes or without prior authorization

Claims submitted without covered diagnosis or procedure codes listed in the policy will be denied; prior authorization is required for benefit coverage of Naglazyme.

When billing, providers must use the most appropriate codes as of the effective date; services not accompanied by covered code(s) will be denied.

Note

Specialist prescribing or consultation required

Naglazyme must be prescribed by or in consultation with a geneticist, endocrinologist, metabolic disorder sub‑specialist, or a physician who specializes in the treatment of lysosomal storage disorders; this specialist involvement is required for approval.

Specialist types specified: geneticist, endocrinologist, metabolic disorder sub‑specialist, or physician specializing in lysosomal storage disorders.

Definitions

Definitive diagnosis of MPS VI

Definitive diagnostic methodsDemonstration of deficient arylsulfatase B (N‑acetylgalactosamine 4‑sulfatase) enzyme activity in leukocytes or fibroblasts.

Alternative molecular confirmationMolecular genetic testing showing biallelic pathogenic or likely pathogenic ARSB variants.

Specimen types for enzyme assayEnzyme activity may be measured in leukocytes or cultured fibroblasts.

Purpose of confirmationDiagnostic confirmation required to establish eligibility for Naglazyme (enzyme replacement therapy) or consideration of hematopoietic stem cell transplantation.

Clinical contextMPS VI diagnosis is supported by clinical features (coarse facies, short stature, kyphoscoliosis, joint stiffness, pulmonary/cardiac disease, hepatosplenomegaly, corneal clouding, hernias) together with biochemical or molecular confirmation.

Background

Mucopolysaccharidosis type VI (MPS VI, Maroteaux–Lamy syndrome) is a rare lysosomal storage disorder caused by deficiency of N‑acetylgalactosamine 4‑sulfatase (arylsulfatase B), leading to accumulation of dermatan sulfate and chondroitin 4‑sulfate. Clinical manifestations are heterogeneous and may include coarse facial features, short stature, kyphoscoliosis, joint stiffness, pulmonary and cardiac disease, hepatosplenomegaly, corneal clouding, and hernias. Definitive diagnosis is by demonstration of deficient arylsulfatase B enzyme activity in leukocytes or fibroblasts or by molecular genetic testing showing biallelic pathogenic or likely pathogenic ARSB variants. Treatment options include enzyme replacement therapy with Naglazyme (galsulfase) or hematopoietic stem cell transplantation.