Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual

Policy #:

2023018

Category:

Pharmacy

Initiated:

May 2023

Last Review:

May 2026

Velmanase alfa-tycv (e.g., Lamzede)

Description:

The policy applies to the following service/procedure: Velmanase alfa-tycv (e.g., Lamzede).

Policy/
Coverage:

Prior Approval is required for Velmanase alfa-tycv (e.g. Lamzede).

The initial use of this drug requires documentation of direct physician involvement (MD/DO) by a physician with specialized training at a center with expertise in the diagnosis and treatment of this rare condition and in the ordering and evaluation, as well as signature, in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.

INITIAL AND CONTINUATION APPROVAL will be for duration of the treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.

Effective May 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Velmanase alfa-tycv (e.g., Lamzede) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered, when ALL the following criteria are met:

INITIAL APPROVAL:

1. Individual is aged 3 years or older (Guffon, 2023); AND

2. Individual has a diagnosis of mild to moderate alpha-mannosidosis and documentation of one of the following is provided (Malm 2019):

a. Deficiency in acid alpha-mannosidase enzyme activity (less than 10% of normal activity) in peripheral blood leukocytes or other nucleated cells such as fibroblasts; OR

b. There is identification off biallelic pathogenic variants in MAN2B1 by molecular gene testing; AND

3. Drug is prescribed for treatment of non-central nervous system disease manifestations (Lamzede, 2023); AND

4. Individual must be able to ambulate independently; AND

5. Individual does not have either of the following:

a. History of a HSCT or bone marrow transplant; OR

b. Diagnosis of severe alpha-mannosidosis.

AUTHORIZATION RENEWAL:

1. Condition stable or improved with treatment (including but not limited to improvement in motor function, improvement in pulmonary function, reduction in serum oligosaccharides) compared to the predicted natural history trajectory of disease; AND

2. Manageable or no side effects.

Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria

Velmanase alfa-tycv (e.g., Lamzede) for any indication or circumstance not described above, does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered.

For members with contracts without Primary Coverage Criteria, velmanase alfa-tycv (e.g., Lamzede) for any indication or circumstance not described above, is considered not Medically Necessary and is not covered or is investigational. Not Medically Necessary or Investigational services are specific contract exclusions in most member benefit certificates of coverage.

DOSAGE AND ADMINISTRATION

For FDA labeled indications, Velmanase alfa-tycv (e.g., Lamzede) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.

The recommended dosage for Velmanase alfa-tycv is1mg/kg (actual body weight) intravenously administered once a week.

Velmanase alfa-tycv (e.g., Lamzede) is available as a 10 mg single dose vial.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

April 22, 2026 to April 30, 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Velmanase alfa-tycv (e.g., Lamzede) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered when the following criteria are met:

Member receives a “recommended” determination from InterQual® criteria review for Velmanase alfa-tycv (e.g., Lamzede) based on diagnosis and requested product. Click the following link to view the InterQual® criteria: https://prod.ds.interqual.com/service/connect/transparency?tid=27b0a724-ca06-4b22-846b-598b8dae52fc

Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria

Velmanase alfa-tycv (e.g., Lamzede) does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered for any indication or circumstance not described above.

For contracts without Primary Coverage Criteria, Velmanase alfa-tycv (e.g., Lamzede) is considered not Medically Necessary and is not covered or is investigational for any indication or circumstance not described above. Not Medically Necessary or Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective May 7, 2025 to April 21, 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Velmanase alfa-tycv (e.g., Lamzede) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is aged 3 years or older; AND

2. There is a diagnosis of mild to moderate alpha-mannosidosis and documentation of one of the following is provided (Malm 2019):

a. Deficiency in acid alpha-mannosidase enzyme activity (less than 10% of normal activity) in peripheral blood leukocytes or other nucleated cells such as fibroblasts; OR

b. There is identification off biallelic pathogenic variants in MAN2B1 by molecular gene testing; AND

3. Drug is prescribed for treatment of non-central nervous system disease manifestations (FDA 2023); AND

4. Must be able to ambulate independently; AND

5. Individual does not have either of the following:

a. History of a HSCT or bone marrow transplant; OR

b. Diagnosis of severe alpha-mannosidosis.

CONTINUED APPROVAL for 1 year:

1. Individual previously met initial approval criteria; AND

2. Documentation shows there is clinically significant improvement or stabilization in clinical signs and symptoms of disease (including but not limited to improvement in motor function, improvement in pulmonary function, reduction in serum oligosaccharides) compared to the predicted natural history trajectory of disease.

Dosage and Administration

Dosing per FDA Guidelines unless otherwise specified below.

The recommended dosage for Velmanase alfa-tycv is1mg/kg (actual body weight) intravenously administered once a week.

Velmanase alfa-tycv (e.g., Lamzede) is available as a 10 mg single dose vial.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Velmanase alfa-tycv (e.g., Lamzede) for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, velmanase alfa-tycv (e.g., Lamzede) for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective May 2024 to May 6, 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is aged 3 years or older; AND

2. There is a diagnosis of mild to moderate alpha-mannosidosis and documentation of one of the following is provided (Malm 2019):

a. Deficiency in acid alpha-mannosidase enzyme activity (<10% of normal activity) in peripheral blood leukocytes or other nucleated cells such as fibroblasts; OR

b. There is identification off biallelic pathogenic variants in MAN2B1 by molecular gene testing; AND

3. Drug is prescribed for treatment of non-central nervous system disease manifestations (FDA 2023); AND

4. Must be able to ambulate independently; AND

5. Individual does not have either of the following:

a. History of a HSCT or bone marrow transplant; OR

b. Diagnosis of severe alpha-mannosidosis; AND

6. Must be dosed in accordance with the FDA label.

CONTINUED APPROVAL for 1 year:

1. Documentation shows there is clinically significant improvement or stabilization in clinical signs and symptoms of disease (including but not limited to improvement in motor function, improvement in pulmonary function, reduction in serum oligosaccharides) compared to the predicted natural history trajectory of disease; AND

2. Must be dosed in accordance with the FDA label.

Dosage and Administration

Dosing per FDA Guidelines

The recommended dosage for Velmanase alfa-tycv is1mg/kg (actual body weight) intravenously administered once a week.

Velmanase alfa-tycv (e.g., Lamzede) is available as a 10 mg single dose vial.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

For members with contracts without primary coverage criteria, velmanase alfa-tycv (e.g., Lamzede®) for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective May 10, 2023 to April 2024

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

Velmanase alfa-tycv (e.g. Lamzede®) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:

1. Individual is aged 3 yrs or older; AND

2. There is a diagnosis of mild to moderate alpha-mannosidosis and documentation of one of the following is provided (Malm 2019):

a. Deficiency in acid alpha-mannosidase enzyme activity (<10% of normal activity) in peripheral blood leukocytes or other nucleated cells such as fibroblasts; OR

b. There is identification off biallelic pathogenic variants in MAN2B1 by molecular gene testing; AND

3. Drug is prescribed for treatment of non-central nervous system disease manifestations (FDA 2023); AND

4. Must be able to ambulate independently; AND

5. Must be dosed in accordance with the FDA label.

CONTINUED APPROVAL for 1 year:

1. Documentation shows there is clinically significant improvement or stabilization in clinical signs and symptoms of disease (including but not limited to improvement in motor function, improvement in pulmonary function, reduction in serum oligosaccharides) compared to the predicted natural history trajectory of disease; AND

2. Must be dosed in accordance with the FDA label.

Dosage and Administration

Dosing per FDA Guidelines

Recommended dosage is:

1mg/kg (actual body weight) intravenously administered once a week.

Velmanase alfa-tycv (e.g., Lamzede®) is available as a 10 mg single dose vial.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Velmanase alfa-tycv (e.g. Lamzede®) for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes including:

1. Individual has a history of a HSCT or bone marrow transplant.

2. Individual cannot walk without support.

3. Individual has a diagnosis of severe alpha-mannosidosis.

For members with contracts without primary coverage criteria, velmanase alfa-tycv (e.g. Lamzede®) for any indication or circumstance not described above, including the following, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

1. Individual has a history of a HSCT or bone marrow transplant.

2. Individual cannot walk without support.

3. Individual has a diagnosis of severe alpha-mannosidosis.

Rationale:

Trial 1

Approval of velmanase alfa (VA) was based on results from the Phase 3 rhLAMAN-05 study (also known as Trial 1; NCT01681953), which was a double-blind, randomized, placebo-controlled study that evaluated VA over 52 weeks at a dose of 1 mg/kg given weekly as an IV infusion. A total of 25 patients were enrolled (14 males, 11 females), including 13 adult patients (age range: ≥18 to 35 years; mean: 25 years) and 12 pediatric patients (age range: ≥6 to <18 years. All patients had alpha-mannosidase activity below 11% of normal and in the range of 8 to 29 µmol/h/mg at baseline. Fifteen patients (8 adult and 7 pediatric) received VA and 10 patients (5 adult and 5 pediatric) received placebo. All patients completed the trial.

The efficacy results for the clinical endpoints assessed at 12 months, 3-minute stair climbing test (3MSCT), 6-minute walking test (6MWT) and forced vital capacity (FVC) (% predicted), favored the VA group and were supported by a reduction in serum oligosaccharide concentration.

The most common adverse reactions reported in Trial 1 (incidence >20%) were nasopharyngitis, pyrexia, headache, and arthralgia. Five serious treatment-emergent adverse events (TEAEs) occurred with VA treatment; however, four of the five serious TEAEs were unrelated to treatment. One case of moderate, acute renal failure considered possibly related to treatment occurred after almost 12 months of treatment in a patient known to be receiving long-term concomitant ibuprofen. VA was temporarily suspended, and the patient recovered after 92 days. The patient restarted active treatment with no safety issues reported. No TEAEs led to discontinuation from the study, and no deaths were reported.

Trial 2 (Pediatric Study)

Velmanase alfa (VA) was also evaluated in a second study, rhLAMAN-08 (also known as Trial 2; NCT02998879), a Phase 2 single-arm trial that included five pediatric patients less than 6 years of age with AM. Patients received velmanase alfa 1 mg/kg as IV infusion once weekly (four patients for 24 months, one patient for 40 months).

The patient’s ranged from 3.7 to 5.9 years of age, with a mean age of 4.5 years. After >24 months of treatment, wt, and height increased in all children (n=5). At baseline and end of the study, most of the patient’s growth percentiles were within the standard range for gender and age, except for one patient’s head circumference that was consistent with a history of macrocephaly and hydrocephalus.

Adverse reactions that occurred in at least two of five patients (and are in addition to the adverse reactions already identified in Trial 1) included cough, otitis media, rhinitis, conjunctivitis, fall, ligament sprain, oropharyngeal pain, swelling face, and upper respiratory tract infection.

VA’s long-term safety and efficacy in children with AM aged less than 6 years was evaluated as well. The safety and tolerability of VA were considered acceptable in all children who participated in the study. Even though all children experienced AEs, most were mild to moderate, and none (IRRs or ADRs) resulted in discontinuation of the study. Efficacy assessment results suggested that long-term treatment with VA may improve serum oligosaccharide levels, hearing impairment, IgG and IgA serum levels, and QoL. Further, children in the study did not demonstrate a marked decline in functional capacity or endurance/physical functioning over the VA treatment period, though additional studies controlling for age-based development are required. The PK profile of VA between the first dose and steady state was comparable.

2024 Update

Annual policy review completed with a literature search using the MEDLINE database through May 2024. No new literature was identified that would prompt a change in the coverage statement.

2025 Update

Annual policy review completed with a literature search using the MEDLINE database through May 2025. No new literature was identified that would prompt a change in the coverage statement.

2026 Update

Annual policy review completed with a literature search using the MEDLINE database through May 2026. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:

References:

Borgwardt L. Guffon N. Amraoui Y, et al(2018) Efficacy and safety of Velmanase alfa in treatment of patients with alpha mannosidosis results from the core and extention phase analysis of phase III multicentre double-blind randomised placebo controlled trial J Inherit Metab Dis 2018;41(6) 1215-1223. doi 10 1007/s 10545-018-0185-0

Borgwardt L. Guffon N. Amraoui Y, et al.(2018) Efficacy and safety of Velmanase alfa in treatment of patients with alpha mannosidosis results from the core and extension phase analysis of phase III multicentre double-blind randomised placebo controlled trial J Inherit Metab Dis 2018;41(6) 1215-1223. doi 10 1007/s 10545-018-0185-0

Guffon N, Konstantopoulou V, Hennermann JB, et al.(2023) Long-term safety and efficacy of velmanase alfa treatment in children under 6 years of age with alpha mannosidosis: A phase2, open label multicenter study (published online ahead of print 2023 Feb 27) J Inherit Metab Dis 2023;10. 1002/jimd 12602, doi:10. 1002/jimd 12602

IDP Analytics(2023) New Drug Review: Lamzede (velmase alfa-tycv) Published online (subscription required) March 2023

IDP(2023) New Drug Review: Lamzede (velmanase alfa-tycv) Published online (subscription required) March 2023

Lamzede (velmanase-alfa-tycv) (package insert) Cary NC: Chiesi USA, Inc 2023

Malm D Nilssen(2001) Alpha-Mannosidosis 2001 Oct 11 (Updated 2019 Jul 18) In:Adam MP, Mirzaa GM, Pagon RA, et al editors GeneReviews (Internet) Seattle (WA); Univ of Washington Seattle; 1993-2023 Available from: https://www.ncbi.nlm.nih.gov/books/NBK1396/ Accessed on: April 23, 2023

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.