Neighborhood Health Plan RI Lamzede Coverage Update

Coverage Criteria for Lamzede (velmanase alfa-tycv)

Initial Approval

Covered when ALL of the following are met:

Initial Approval Criteria: Patient is between 3 and 35 years of age; medication is prescribed by or in consultation with a specialist familiar with treatment of lysosomal storage disorders; documented baseline serum oligosaccharides; documented baseline age-appropriate values for one or more functional measures (e.g., 6-MWT, 3-MSCT, pulmonary function tests such as FVC % predicted, motor function tests); definitive diagnosis of alpha-mannosidosis confirmed by BOTH identification of deficient acid alpha-mannosidase enzyme activity in peripheral blood leukocytes or other nucleated cells (e.g., fibroblasts) with activity <10% of normal AND identification of biallelic pathogenic variants in MAN2B1 by molecular genetic testing; patient has signs and symptoms consistent with mild or moderate alpha-mannosidosis (for example absence of neurological manifestations and able to ambulate independently); therapy is intended to treat non-central nervous system manifestations of alpha-mannosidosis; if female of reproductive potential, confirmed negative pregnancy test.age 3-35 years

Applies to initial approvals

Renewal

Renewal criteria — all required:

Renewal Criteria: Patient continues to meet the initial approval criteria; absence of unacceptable toxicity from the drug (examples include anaphylaxis or severe allergic/infusion-associated reactions); patient has demonstrated beneficial response or stabilization compared to pretreatment baseline in one or more of: serum oligosaccharide concentration, 6-minute walk test (6-MWT), 3-minute stair climb test (3-MSCT), forced vital capacity (FVC) % predicted, or slowing/stabilization of clinical decline.demonstrated benefit or stabilization

Renewal granted for additional six-month periods

Investigational Use Exclusion

Not covered when:

Investigational or unapproved uses: Use at a dose or for a condition other than FDA-approved indications or those recognized by standard compendia (AHFS-DI, Thomson Micromedex DrugDex, Clinical Pharmacology, Wolters Kluwer Lexi-Drugs, or peer-reviewed literature) is considered investigational and not covered.N/A

Per policy investigational use exclusion

Explicit denial conditions: Coverage will not be provided if patient cannot walk without support; has a history of hematopoietic stem cell transplantation (HSCT) or bone marrow transplant; presence of a known chromosomal abnormality or syndrome affecting psychomotor development other than alpha-mannosidosis; or total IgE >800 IU/mL.N/A

Per policy explicit denial conditions

Coverage will not be provided when any of the following apply: the patient cannot walk without support; the patient has a documented history of hematopoietic stem cell transplant (HSCT) or bone marrow transplant; the patient has a known chromosomal abnormality or syndrome affecting psychomotor development other than alpha-mannosidosis; or the patient has a total serum IgE >800 IU/ml. These exclusions are applied during review of initial and renewal requests and must be documented in the medical record.

Use of therapy or supportive testing for a dose or condition that is not a recognized medically accepted indication is considered investigational and is not covered. Investigational use is defined by lack of support in standard reference compendia (e.g., AHFS‑DI, DrugDex, Clinical Pharmacology, Lexi‑Drugs) or sufficient peer‑reviewed evidence. Requests for treatment or testing intended to support investigational or off‑label indications will be denied.

Confirmation of alpha-mannosidosis to establish eligibility for enzyme replacement therapy with Lamzede

Required diagnostic confirmation to establish eligibility for enzyme replacement therapy with Lamzede:

Diagnostic Confirmation for Alpha‑mannosidosis: Definitive diagnosis requires BOTH: identification of deficient acid alpha-mannosidase enzyme activity in peripheral blood leukocytes or other nucleated cells (e.g., fibroblasts) with activity <10% of normal; AND identification of biallelic pathogenic variants in MAN2B1 by molecular genetic testing.

Both enzyme assay and molecular testing must be documented prior to coverage

Billing and Diagnosis Codes

Covered HCPCS CodesHCPCSCovered

J0217

Injection, velmanase alfa-tycv, 1 mg; 1 billable unit = 1 mg

NDCNDC

10122-0180-xX

Lamzede 10 mg as a lyophilized powder in a SDV for reconstitution: 10122-0180-xX

Covered Diagnosis CodesICD-10Covered

E77.1

Defects in glycoprotein degradation

Maximum per-dose unit

Maximum per‑dose unit110 mg (110 units) every 7 days

HCPCS unit mapping1 billable unit = 1 mg (use HCPCS J0217 for billing)

Dosing frequencyOnce weekly (every 7 days)

Provider Requirements and Actions

Prior Authorization

Prior Authorization Required

Prior Authorization Required. Prior authorization is required before initiation of therapy. Initial approval is for six months; renewals may be granted for additional six-month periods. Dose/frequency: administered as an intravenous infusion once weekly at the FDA‑approved mg/kg dosing (actual body weight).

Initial authorization length: 6 months
Renewal authorization length: 6 months
Dosing frequency: once weekly IV

Step Therapy

Therapy Sequencing Intent

Therapy should be used in accordance with FDA labeling and the plan’s clinical coverage criteria. The intent of these requirements is to ensure use for a medically accepted indication and, when applicable, to encourage use of other appropriate, cost‑effective options first. For Medicare members, plan criteria apply only in the absence of an applicable NCD or LCD.

Use per FDA‑approved labeling and relevant clinical literature

Member Eligibility Requirements

To be eligible for coverage, members must meet the policys initial approval criteria: be between 3 and 35 years of age; have the medication prescribed by or in consultation with a specialist experienced in lysosomal storage disorders; have documented baseline serum oligosaccharides and baseline age‑appropriate functional measure(s) (e.g., 6‑MWT, 3‑MSCT, pulmonary function testing, motor function testing); have a definitive diagnosis confirmed by BOTH an acid alpha‑mannosidase enzyme assay showing <10% of normal activity in peripheral blood leukocytes or other nucleated cells and molecular genetic testing identifying biallelic pathogenic MAN2B1 variants; have signs/symptoms consistent with mild or moderate alpha‑mannosidosis (for example, able to ambulate independently and absence of neurologic manifestations); therapy must be intended to treat non‑CNS manifestations; and, for females of reproductive potential, a confirmed negative pregnancy test.

Not Covered / Limitations

Genetic or enzyme testing performed solely to support investigational or off‑label uses that are not recognized by standard compendia will not establish coverage for therapy. In other words, identification of variants or enzyme results intended to justify treatment for non‑approved indications or dosing does not meet the policys requirements for covered use.

Background on Alpha-mannosidosis and Lamzede

Alpha‑mannosidosis is an ultra‑rare lysosomal storage disorder caused by deficient acid alpha‑mannosidase activity due to biallelic pathogenic variants in MAN2B1, leading to intracellular oligosaccharide accumulation and multisystem manifestations including recurrent infections, motor and cognitive impairment, hearing loss, and musculoskeletal involvement. Lamzede (velmanase alfa‑tycv) is indicated to treat the non‑central nervous system manifestations of alpha‑mannosidosis; this policy requires biochemical and molecular confirmation of disease (enzyme activity <10% plus biallelic MAN2B1 pathogenic variants) and baseline functional and biochemical measures prior to authorization.

Definitions

Alpha-mannosidosis (AM)

DefinitionAlpha-mannosidosis (AM) is an ultra-rare lysosomal storage disorder caused by deficient activity of the enzyme alpha-mannosidase due to biallelic pathogenic variants in MAN2B1 (MANZB1 in source), leading to intracellular accumulation of oligosaccharides and multisystem manifestations.

Core clinical featuresVariable symptoms including recurrent infections, cognitive and speech impairment, muscular weakness, joint abnormalities, ataxia, hearing loss, and distinctive facial features.

Indication for therapyLamzede (velmanase alfa-tycv) is indicated for treatment of non‑central nervous system manifestations of AM in pediatric and adult patients.

EpidemiologyEstimated prevalence approximately 1 in 500,000 to 1 in 1,000,000 individuals worldwide.

OpenPayer

Lamzede (velmanase alfa-tycv) (Intravenous) – Coverage Criteria for Alpha‑Mannosidosis