Pharmacy Prior Authorization Criteria

Lenmeldy (atidarsagene autotemcel)

Indications for Prior Authorization

Lenmeldy (atidarsagene autotemcel)

• For diagnosis of Metachromatic Leukodystrophy (MLD)
  Indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). The safety and efficacy of LENMELDY have not yet been established in children with the late juvenile form of the disease.

Criteria

Lenmeldy

Prior Authorization

Length of Approval: 1 Time Authorization in Lifetime*

• Submission of medical records (e.g., chart notes) confirming both of the following:
• Diagnosis of metachromatic leukodystrophy (MLD)
AND
• Disease is confirmed by all of the following [A, B]:
• Presence of biallelic pathogenic arylsulfatase A (ARSA) gene mutation as detected by an FDA-approved test or a test performed at a facility approved by Clinical Laboratory Improvement Amendments (CLIA)
• Elevated sulfatide levels (e.g., elevated urinary sulfatide excretion, elevated sulfatide levels in dried blood spots [DBS])
• Low or residual ARSA activity (e.g., enzyme activity below 1% of wildtype activity, deficient ARSA activity in leukocytes or fibroblasts on lysosomal enzyme screen) [C]
AND
• Disease is one of the following [D]:
• Pre-symptomatic late infantile (PSLI) as confirmed by both of the following:
• Disease onset at less than or equal to 30 months (2.5 years) of age
AND
• One of the following:
• Absence of neurological signs and symptoms of MLD (e.g., peripheral neuropathy, gait difficulties, hypotonia)
• Abnormal reflexes or abnormalities on brain magnetic resonance imaging (MRI) and/or nerve conduction tests not associated with functional impairment (e.g., no tremor, no peripheral ataxia)
OR
• Pre-symptomatic early juvenile (PSEJ) as confirmed by both of the following:
• Disease onset at greater than 30 months (2.5 years) and less than 7 years of age
AND
• One of the following:
• Absence of neurological signs and symptoms of MLD (e.g., peripheral neuropathy, gait difficulties, hypotonia)
• Abnormal reflexes and/or clonus or abnormalities on brain magnetic resonance imaging (MRI) and/or nerve conduction tests not associated with functional impairment (e.g., no tremor, no peripheral ataxia)
OR
• Early-symptomatic early juvenile (ESEJ) as confirmed by all of the following:
• Disease onset at greater than 30 months (2.5 years) and less than 7 years of age
• Gross motor function classification (GMFC)-MLD score less than or equal to 1
• Intelligence quotient (IQ) of greater than or equal to 85
AND
• Prescribed by or in consultation with a specialist with expertise in the diagnosis and treatment of MLD at an authorized treatment center for Lenmeldy with shared-decision-making regarding treatment risks
AND
• Provider attests to both of the following:
• Patient has never received Lenmeldy treatment in their lifetime*
• Patient has never received prior hematopoietic stem cell transplant (HSCT)

P & T Revisions

2026-06-10, 2026-05-07, 2025-05-09, 2024-05-16

References

1. Lenmeldy Prescribing Information. Orchard Therapeutics. Boston, MA. August 2025.
2. Asbreuk MABC, Schoenmakers DH, Adang LA, et al. Metachromatic leukodystrophy. Neurology. 2025; 105(2):e213817.
3. Bonkowsky JL, Firth HV, Dashe JF. Metachromatic leukodystrophy. Wolters Kluwer. Updated March 19, 2026. Accessed April 15, 2026. Available from: https://www.uptodate.com.
4. Adang LA, Bonkowsky JL, Boelens JJ, et al. Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States. Cytotherapy. 2024; 26(7):739-748.

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End Notes

1. Metachromatic leukodystrophy (MLD) is a rare, progressive neurodegenerative disorder caused by biallelic pathogenic variants in the ARSA gene, which leads to reduced arylsulfatase A (ASA) activity and subsequent accumulation of sulfate-containing glycosphingolipids called sulfatides that accumulate in the membranous structures of the central and peripheral nervous systems. [2-4]
2. The combination of low ARSA activity, elevated sulfatide levels, and genotype definitely establishes MLD diagnosis. Ruling out differential diagnoses is crucial in Lenmeldy treatment decisions as there are currently no gene therapy options available to treat SapB-dependent MLD or MSD. Non-pathogenic pseudodeficiency alleles in the ARSA gene can result in low enzyme activity similar to MLD, thus MLD diagnosis requires sulfatide levels coupled with ARSA enzyme activity. Other leukodystrophies such as adrenoleukodystrophy, Alexander disease, Canavan disease, Tay-Sachs disease, and Krabbe disease cannot be differentiated from MLD based on biochemical testing alone and require genetic testing to determine diagnosis. [2-4]
3. All patients with MLD have reduced enzymatic activity, but there are no standardized thresholds to stratify severity. ARSA activity can vary depending on whether patients demonstrate cognitive, motor, or mixed disease presentation. Residual ARSA activity below 1% of wildtype is strongly associated with early-onset MLD. [2, 4]
4. MLD is classified into the following subtypes depending on age of disease onset: late-infantile (onset is before 30 months), early-juvenile (onset is between 2.5 and 6 years), late-juvenile (onset is between 7 and 16 years), and adult (onset is at 16 years or later). Lenmeldy is not indicated for use in children with the late juvenile form of the disease. [2, 4]

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Revision History

• 2026-06-10: Annual Review 2026 - Update to require medical records confirming MLD diagnosis and disease-confirming biomarkers. Specified ARSA mutation is biallelic pathogenic mutation with standard testing verbiage. Added confirmatory biomarkers: elevated sulfatide levels and deficient ARSA activity. Added 2.5 years of age after 30 months within criteria for clarity. Added allowance for clonus without functional impairment to PSEJ subcriteria. Updated prescriber specialist requirement for standard gene therapy specialist verbiage to include SDM of treatment risks.
• 2026-05-07: Annual Review 2026 - Update to require medical records confirming MLD diagnosis and disease-confirming biomarkers. Specified ARSA mutation is biallelic pathogenic mutation with standard testing verbiage. Added confirmatory biomarkers: elevated sulfatide levels and deficient ARSA activity. Added 2.5 years of age after 30 months within criteria for clarity. Added allowance for clonus without functional impairment to PSEJ subcriteria. Updated prescriber specialist requirement for standard gene therapy specialist verbiage to include SDM of treatment risks.
• 2025-05-09: 2025 Annual Review. No updates.
• 2024-05-16: New Program

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