ModifiedmhnPolicy CP.PHAR.601

Velmanase Alfa (Lamzede) — Coverage Criteria

Medical necessity criteria, dosing, and authorization rules for velmanase alfa (Lamzede) to treat non-central nervous system manifestations of alpha-mannosidosis for commercial, HIM/ICHRA, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyVelmanase Alfa (Lamzede) — Coverage Criteria

Policy CodePolicy CP.PHAR.601

Key ActionSubmit prior authorization with documentation confirming diagnosis, prescribing specialist involvement, absence of CNS manifestations, current weight, and dosing ≤ 1 mg/kg/week.

Change TypeMaterial criteria and authorization updates

Effective DateFeb 16, 2023

Next Review DateN/A

SourceLink

POLICY UPDATE CHANGES

Updated initial and continued approval durations from 6 months to 12 months for Medicaid/HIM/ICHRA and added standard authorization duration language for Commercial; added ICHRA line of business.

Added examples of CNS manifestations to Initial Approval criteria and examples of positive treatment response to Continued Therapy (previously in Appendix D).

Added/updated HCPCS code in coding section.

12 moApproval duration (Medicaid/HIM/ICHRA)

6 moApproval duration (Commercial)

1 mg/kg/wkMaximum dose

J0217HCPCS

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Coverage Criteria for Velmanase alfa (Lamzede)

Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met:

Initial Approval - Alpha-Mannosidosis: 1. Diagnosis of AM confirmed by one of the following: (a) reduced AM activity < 10% of normal in leukocytes or fibroblasts OR (b) genetic testing showing biallelic MAN2B1 mutation; 2. Prescribed by or in consultation with an endocrinologist, neurologist, ophthalmologist, clinical geneticist, or specialist familiar with treatment of lysosomal storage disorders; 3. Member does not have central nervous system (CNS) manifestations of AM (examples: mental retardation, speech delay, sensorineural hearing loss, dysostosis multiplex, genu valgum, hypotonia, motor and coordination disturbances, ataxia, ocular manifestations with strabismus, acute psychotic manifestations, occipital white matter signal aberrations, delayed myelination, hydrocephalus); 4. Member is able to ambulate independently; 5. Member has not previously received a bone marrow transplant or hematopoietic stem cell transplantation; 6. Documentation of current actual body weight in kg; 7. Dose does not exceed 1 mg/kg (actual body weight) per week.

All conditions must be met for initial approval.

Continuation Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met:

Continued Therapy - Alpha-Mannosidosis: 1. Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; OR (b) currently receiving medication and enrolled in a state/product with continuity of care regulations; 2. Member is responding positively to therapy as evidenced by stabilization or improvement in at least one of the following parameters (examples: serum oligosaccharides levels; 3-minute stair climb test; 6-minute walk test; Bruininks-Oseretsky test of motor proficiency; forced vital capacity; coarse facial features; frequency of infections due to immune deficiency; skeletal abnormalities); 3. Documentation of current actual body weight in kg; 4. If request is for a dose increase, new dose does not exceed 1 mg/kg (actual body weight) per week.

All conditions must be met for continuation.

Authorization duration and illustrative examples — policy criteria updates and references to main criteria

Policy criteria were updated; see main criteria sections for full logic.

Authorization durations: Initial and continued approval durations updated: Medicaid/HIM/ICHRA — 12 months; Commercial — standard authorization duration language (commercial/renewal per plan).12 months

2Q 2026 updates: initial and continued approval durations changed from 6 to 12 months for Medicaid/HIM; ICHRA added as line of business. Examples of CNS manifestations were added to Initial Approval and examples of positive treatment response were added to Continued Therapy (previously in Appendix D).

Requests for use of velmanase alfa for indications that are not FDA-approved and not specifically addressed in this policy will be excluded unless the provider submits sufficient supporting documentation demonstrating efficacy and safety. Off‑label requests must follow the applicable off‑label use policies: CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace/ICHRA, and CP.PMN.53 for Medicaid, or be supported by an applicable evidence of coverage document.

When there is a conflict between this clinical policy and a state Medicaid coverage provision for a Medicaid member, the state Medicaid coverage provision takes precedence. Providers should consult the applicable state Medicaid manual for specific coverage rules, exclusions, or differences that apply to Medicaid members.

Velmanase alfa is indicated for non‑central nervous system manifestations of alpha‑mannosidosis; use for patients with CNS manifestations listed in the Initial Approval criteria (examples include mental retardation, speech delay, sensorineural hearing loss, dysostosis multiplex, genu valgum, hypotonia, motor and coordination disturbances, ataxia, ocular manifestations with strabismus, acute psychotic manifestations, occipital white matter signal aberrations, delayed myelination, and hydrocephalus) is not covered under the indication in this policy.

This clinical policy is intended as a guide to medical necessity and assists in coverage determinations; it does not constitute a contract or guarantee of payment. Coverage decisions remain subject to the member’s evidence of coverage, certificate of coverage, contract terms, exclusions, limitations, and applicable state or federal requirements. Providers must supply documentation (e.g., chart notes, lab results) supporting that the member meets all medical necessity criteria; failure to provide required documentation or to follow applicable off‑label policies may result in denial.

Coding and Dosing Information

HCPCS CodesHCPCS

J0217

Injection, velmanase alfa-tycv, 1 mg

Updated HCPCSHCPCS

HCPCS (updated)

HCPCS code for velmanase alfa updated in coding section

inv-10: Maximum dose —

Maximum recommended doseDose does not exceed 1 mg/kg (actual body weight) per week

Dosing frequencyAdminister IV once every week

Weight basisDose calculated using current actual body weight in kilograms

Prior Authorization, Documentation, and Provider Expectations

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation supporting that the member meets all approval criteria before Lamzede (velmanase alfa-tycv) will be authorized.

Affected diagnoses: Alpha‑mannosidosis (see Initial Approval and Continued Therapy criteria).
Prescriber: Prescribed by or in consultation with an endocrinologist, neurologist, ophthalmologist, clinical geneticist, or specialist familiar with lysosomal storage disorders.
Diagnostic confirmation required: either reduced alpha‑mannosidase activity < 10% in leukocytes or fibroblasts, or genetic testing showing biallelic MAN2B1 mutation.
Exclusion of CNS manifestations: member must NOT have central nervous system manifestations of AM (examples include mental retardation, speech delay, sensorineural hearing loss, dysostosis multiplex, genu valgum, hypotonia, motor/coordination disturbances, ataxia, ocular manifestations with strabismus and acute psychotic manifestations, occipital white matter signal aberrations, delayed myelination, hydrocephalus).
Functional status: member must be able to ambulate independently.
Transplant history: no prior bone marrow transplant or hematopoietic stem cell transplantation.
Weight documentation: current actual body weight in kg must be provided.

Background

Alpha‑mannosidosis (AM) is a rare lysosomal storage disorder caused by deficient alpha‑mannosidase activity or biallelic MAN2B1 mutations. Velmanase alfa is a recombinant human alpha‑mannosidase indicated to treat the non‑CNS manifestations of AM in adults and pediatric patients. Individual non‑CNS manifestations can include coarse facial features, recurrent infections related to immune deficiency, and skeletal abnormalities; central nervous system features (listed in the policy) are excluded from coverage under this indication.

Definitions and Key Terms

inv-20: Alpha-mannosidosis (AM) — definition and clinical presentation (non-CNS vs CNS)

DefinitionAlpha-mannosidosis (AM) is a lysosomal storage disorder characterized by deficient alpha-mannosidase activity or biallelic MAN2B1 mutations

Non-CNS clinical featuresMay include coarse facial features, frequent infections due to immune deficiency, and skeletal abnormalities

CNS clinical features (examples)May include mental retardation, speech delay, sensorineural hearing loss, dysostosis multiplex, genu valgum, hypotonia, motor/coordination disturbances, ataxia, ocular manifestations with strabismus, acute psychotic manifestations, occipital white matter signal aberrations, delayed myelination, and hydrocephalus

inv-21: Dosing regimen — 1 mg/kg IV once weekly; maximum dose 1 mg/kg/week

Dose per administration1 mg/kg (actual body weight) IV once weekly