Medicare Advantage

Medical Policy

Title:

Velmanase alfa (Lamzede)

Policy #:

MA08.147

Policy

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

MEDICALLY NECESSARY

Initial criteria

Velmanase alfa-tycv (Lamzede) is considered medically necessary and, therefore, covered for the treatment of non–central nervous system manifestations (e.g., skeletal abnormalities, myopathy, motor function disturbances, immunodeficiency) of alpha-mannosidosis (AM) in pediatric and adult individuals when all of the following criteria are met, including dosing and frequency:

The individual is at least 3 years old
Prescribed by or in consultation with a geneticist or metabolic specialist
Diagnosis is confirmed by either of the following:

Confirmation of diagnosis by biochemical assay showing decreased alpha-mannosidase activity in white blood cells or skin fibroblasts less than 10 percent of normal values
Genotyping revealing two pathogenic mutations of the MAN2B1 gene

Documented baseline age-appropriate values for one or more of the following:

6-minute walk test (6-MWT)
3-minute stair climb test (3-MSCT)
Pulmonary function tests (e.g., forced vital capacity [FVC]),
Motor function (i.e., Bruininks-Oseretsky Test of Motor Proficiency [BOT-2] )

The individual does not have any of the following:

A history of a hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation
The individual cannot walk without support

Dosing and frequency: children, adolescents and adults dosing intravenous infusion: 1 mg/kg once every week

NOTE: For very young individuals in whom FVC or 6-MWT are not suitable for measuring, requests will be reviewed on a case-by-case basis.

Continuation criteria

The individual continues to meet the initial criteria
The individual has demonstrated a beneficial response to therapy or stabilization of disease compared to pretreatment age-appropriate baseline values in one or more of the following:

Stability or improvement in serum oligosaccharide concentration
Stability or improvement in 6-MWT
Stability or improvement in 3-MSCT
Stability or improvement in FVC (% predicted)
Stabilization or slowing in the rate of disease progression or clinical decline

EXPERIMENTAL/INVESTIGATIONAL

All other uses of velmanase alfa-tycv (Lamzede) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of velmanase alfa-tycv (Lamzede). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to, the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of velmanase alfa-tycv (Lamzede) outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member's dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the utilization management activities. The Company reserves the right to conduct postpayment review and audit procedures for any claims submitted for velmanase alfa-tycv (Lamzede).

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of velmanase alfa-tycv (Lamzede) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the company that supports this request.

Guidelines

There is no Medicare policy addressing this service; therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, velmanase alfa-tycv (Lamzede) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when velmanase alfa-tycv (Lamzede) is covered under a member's medical benefit (Part B benefit). It does not address instances when velmanase alfa-tycv (Lamzede) is covered under a member’s pharmacy benefit (Part D benefit).

FOR MEDICARE ADVANTAGE POLICIES BASED ON COMMERCIAL POLICY IN WHICH THERE IS NO LCD, NCD, OR OTHER MEDICARE RESOURCE:

There is no Medicare coverage determination addressing velmanase alfa-tycv (Lamzede); therefore, the Company policy is applicable.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

TESTING

3-Minute Stair Climbing Test (3-MSCT)

The 3-MSCT is a physical test used to measure functional capacity and endurance. Individuals are asked to climb as many stairs as possible in 3 minutes; the result is often used to track disease progression or improvement in response to treatment.

6-Minute Walking Test (6-MWT)

The 6-MWT is a submaximal exercise test that measures aerobic capacity and endurance. The distance that an individual can quickly walk on a flat, hard surface in a period of 6 minutes is measured.

Forced Vital Capacity (FVC)

FVC is a measure of the amount of air an individual can exhale forcefully and quickly after taking a deep breath.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, velmanase alfa-tycv (Lamzede) is covered under the medical benefits of the Company's products when the medical necessity criteria including dosing and frequency requirements listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

On February 16, 2023, the FDA approved velmanase alfa-tycv (Lamzede), the first enzyme-replacement therapy (ERT) approved in the United States for the treatment of non–central nervous system manifestations of alpha-mannosidosis (AM) in adult and pediatric individuals.

GERIATRIC USE

The safety and effectiveness of velmanase alfa-tycv (Lamzede) has not been established in individuals 65 years of age and older.

INDICATIONS AND USAGE

Velmanase alfa-tycv (Lamzede) is indicated for the treatment of non–central nervous system manifestations of AM in adult and pediatric patients.

Description

Alpha-mannosidosis (AM) is an ultra-rare, progressive genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. The estimated prevalence of AM is one in every 500,000 individuals worldwide. Symptoms vary widely in type and severity from one person to another, but may include recurrent infections, hearing impairment, impairment of mental function and speech, muscular weakness, joint abnormalities, ataxia, and distinctive facial features. AM is caused by mutations of the MAN2B1 gene. This genetic mutation is inherited as an autosomal recessive trait.

AM is best thought of as a continuum of disease that is generally broken down into three forms: a mild, slowly progressive form (type 1); a moderate form (type 2); and a severe, often rapidly progressive and potentially life-threatening form (type 3).

AM belongs to a group of diseases known as the lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that function as the primary digestive units. Enzymes within the lysosomes break down or digest particular nutrients, such as complex molecules composed of a sugar attached to a protein (glycoproteins). Low levels or inactivity of the alpha-mannosidase enzyme leads to the abnormal accumulation of compounds upstream in the metabolic pathway in the cells of affected individuals, with unwanted consequences.

Velmanase alfa-tycv (Lamzede) is the first and only FDA-approved treatment for AM. Velmanase alfa-tycv (Lamzede) does not cross the blood–brain barrier and therefore is not expected to treat the neurological aspects of the disease. Prior to the approval of velmanase alfa-tycv (Lamzede), treatment of AM was primarily symptomatic. Some individuals may benefit from allogeneic hematopoietic stem cell transplantation (HSCT). Those most likely to benefit from HSCT are younger individuals in whom significant complications have not yet developed.

The approval of velmanase alfa-tycv (Lamzede) was based on a Phase 3, randomized, double-blind, placebo-controlled trial in 25 individuals 6 to 35 years of age (NCT01681953). Individuals treated with velmanase alfa-tycv (Lamzede) performed better than those receiving placebo in outcomes such as the 3-minute stair climbing test, 6-minute walking test, and forced vital capacity.

Velmanase alfa-tycv (Lamzede) binds to extracellular mannose-6-phosphate receptors and is transported to lysosomes, where it provides an exogenous source of alpha-mannosidase. Alpha-mannosidase degrades mannose-containing oligosaccharides; lack of this enzyme leads to the accumulation of mannose-rich oligosaccharides in tissue, which causes clinical symptoms associated with AM lysosomal storage disease.

Velmanase alfa-tycv (Lamzede) is administered as a once-weekly intravenous infusion. Dosing of velmanase alfa-tycv (Lamzede) is weight based; therefore, pricing may vary significantly for each individual.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

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

Ceccarini MR, Codini M, Conte C, et al. Alpha-Mannosidosis: Therapeutic Strategies. Int J Mol Sci. 2018;19(5):1500.

Elsevier's Clinical Pharmacology Compendium. Lamzede (velmanase alfa-tycv). [Clinical Pharmacology Web site]. 03/01/2023. Available at: https://www.clinicalkey.com/pharmacology/monograph/5441?n=LAMZEDE. [via subscription only]. Accessed December 21, 2023.

Lamzede (velmanase alfa) [prescribing information]. Parma, Italy: Chiesi Farmaceutici S.p.A.; February 2023. Available at: https://www.lamzede.com/. Accessed December 21, 2023.

Lexi-Drugs Compendium. Lamzede (velmanase alfa-tycv). [Lexicomp Online Web site]. 12/29/23. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7308716?cesid=6cEPIlF2ibV&searchUrl=/lco/action/search?q=Lamzede&t=name&acs=false&acq=Lamzede#doa. [via subscription only]. Accessed December 21, 2023.

Malm D, Nilssen O. Alpha-Mannosidosis. GeneReviews® [NIH National Library of Medicine Web site]. October 11, 2001. Updated July 18, 2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1396/. Accessed December 21, 2023.

MedlinePlus. Alpha-mannosidosis. National Library of Medicine. [MedlinePlus Web site]. May 1, 2014. Available at: https://medlineplus.gov/genetics/condition/alpha-mannosidosis/#references. Accessed December 21, 2023.

Micromedex®. Lamzede (velmanase alfa-tycv). [Micromedex Web site]. 08/12/2023. Available at: https://www.micromedexsolutions.com/micromedex2/librarian/CS/5458BB/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/6F5AED/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.GoToDashboard?docId=933966&contentSetId=100&title=Velmanase+Alfa-tycv&servicesTitle=Velmanase+Alfa-tycv&brandName=Lamzede&UserMdxSearchTerm=Lamzede&=null#quickanspanelprint. [via subscription only]. Accessed December 21, 2023.

National Institutes of Health (NIH). Genetic and Rare Diseases Information Center (GARD) Alpha-mannosidosis. [NIH Web site]. Available at: https://rarediseases.info.nih.gov/diseases/6968/alpha-mannosidosis. Accessed December 21, 2023.

National Organization for Rare Disorders (NORD). Alpha-Mannosidosis. [NORD Web site]. 08/13/2018. Available at: https://rarediseases.org/rare-diseases/alpha-mannosidosis/. Accessed December 21, 2023.

Santoro L, Zampini L, Padella L, et al. Early biochemical effects of velmanase alfa in a 7-month-old infant with alpha-mannosidosis. JIMD Rep. 2020;55(1):15-21.

US Food and Drug Administration (FDA). FDA approves first enzyme replacement therapy for rare alpha-mannosidosis. [FDA Web site]. 02/17/2023. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-enzyme-replacement-therapy-rare-alpha-mannosidosis. Accessed December 21, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Lamzede (velmanase alfa-tycv) Biologics License Application (BLA) Approval. Product approval information. [FDA Web site]. 02/16/2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761278Orig1s000ltr.pdf. Accessed December 21, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Lamzede (velmanase alfa-tycv). Prescribing information. [FDA Web site]. 02/16/2023.Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761278s000lbl.pdf. Accessed December 21, 2023.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

E77.1 Defects in glycoprotein degradation

HCPCS Level II Code Number(s)

J0217 Injection, velmanase alfa-tycv, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.147:

05/28/2025	This policy has been reviewed and reissued to communicate the Company's continuing position on velmanase alfa-tycv (Lamzede).
03/11/2024	New policy #MA08.147 will become effective on 03/11/2024. The policy has been developed to communicate the Company’s coverage position for velmanase alfa-tycv (Lamzede) and is based on FDA labeling.

Version Effective Date:

3/11/2024

Version Issued Date: