CurrentBlue Cross Blue Shield - MassachusettsPolicy 106

Atidarsagene autotemcel (Lenmeldy) for metachromatic leukodystrophy

Medical necessity and prior authorization policy for atidarsagene autotemcel (Lenmeldy) for treatment of metachromatic leukodystrophy (MLD) for eligible Blue Cross Blue Shield - Massachusetts members.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyAtidarsagene autotemcel (Lenmeldy) for metachromatic leukodystrophy

Policy CodePolicy 106

Change TypeNo material clinical or coverage changes in this revision.

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization requests via Authorization Manager and complete the Lenmeldy prior authorization form (Policy 109) with required diagnostic documentation.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

1 injectionlifetime dosing limit

J3391HCPCS

E75.25ICD-10

4.2–9×10^6min dose

30×10^6max dose

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Coverage and Medical Necessity Criteria

Medical Necessity Criteria

Covered when ALL of the following are met

Main eligibility: Confirmed diagnosis of metachromatic leukodystrophy (MLD) by gene sequencing and/or deletion/duplication assessment identifying biallelic ARSA pathogenic or likely pathogenic variants.

Proband biochemical confirmation (if proband): If a proband individual, all of the following: (a) ARSA enzyme activity in leukocytes below reference values; (b) Urinary sulfatide levels above reference values.

FDA label normal ARSA range cited in Policy Guidelines; laboratory-specific sulfatide reference ranges may vary.

Permitted clinical subtypes: Confirmed diagnosis of one of the following MLD subtypes: (a) Pre-symptomatic late infantile; (b) Pre-symptomatic early juvenile; (c) Early symptomatic early juvenile.

See Policy Guidelines for trial-based subtype definitions (age cutoffs, genotype and symptom definitions).

Transplant/institutional requirements: Meets institutional requirements for a stem cell transplant procedure where the individual is expected to receive gene therapy, which may include adequate performance status, absence of advanced liver disease, adequate eGFR, adequate DLCO, adequate LVEF, and absence of clinically significant active infections.

Institutional transplant eligibility per treating center protocols.

No prior transplant or gene therapy: No prior allogeneic hematopoietic stem cell transplant (HSCT) or prior gene therapy.

Repeat treatment with atidarsagene autotemcel is considered investigational.

Covered Indications (trial-matched populations)

Covered when ALL of the following are met (based on trial populations demonstrating benefit):

Population and diagnosis: Patient has MLD confirmed by biallelic ARSA pathogenic variants plus biochemical confirmation (deficient ARSA activity and elevated urinary sulfatides).

Genetic testing alone sufficient for siblings of an index case per Policy Guidelines.

Age and symptom-status groups eligible: Patient is in one of the trial-enrolled groups: pre-symptomatic late infantile MLD, pre-symptomatic early juvenile MLD, or early symptomatic early juvenile MLD.Late infantile: expected disease onset ≤30 months; Early juvenile: expected/actual onset >30 months and <7 years; Early symptomatic defined as walking independently and IQ ≥85.

Trial classifications and definitions per study enrollment criteria.

Treatment rationale: Treatment intent and entry characteristics align with trial evidence (provider documents that the patient meets entry characteristics similar to trial populations to improve motor/cognitive outcomes or slow progression).

Not Medically Necessary / Investigational

Not covered / investigational when ANY of the following apply:

Non-matching disease stage: Patients with disease stages not represented in the trials, including late infantile or early juvenile patients symptomatic beyond the early symptomatic entry criteria, or late-onset forms not studied.

Allogeneic HSCT is ineffective for late infantile or early juvenile forms; evidence uncertain outside trial-defined groups.

Lack of diagnostic confirmation: Absence of genetic confirmation of biallelic ARSA pathogenic variants, or missing biochemical confirmation when not a sibling of an index case.

ARSA pseudodeficiency should be excluded; genetic testing alone may suffice for siblings per Policy Guidelines.

Atidarsagene autotemcel (Lenmeldy) is considered investigational for any indication that does not meet the specific medical necessity criteria listed above. This includes use when diagnostic confirmation, subtype eligibility, institutional/transplant procedure requirements, or prior-treatment exclusions are not satisfied. Repeat administration of atidarsagene autotemcel is also considered investigational.

Allogeneic hematopoietic stem cell transplant (HSCT) has yielded mixed results across MLD subtypes and, based on available evidence, has been found to be ineffective for late infantile or early juvenile forms and is not recommended for these populations.

Use of atidarsagene autotemcel is considered investigational when the policy's stated criteria are not met. If the patient lacks genetic or biochemical confirmation, is outside the specified age/symptom groups, fails institutional/transplant eligibility, or has previously received allogeneic HSCT or prior gene therapy, the treatment is investigational and not covered under this policy.

Evidence indicates that allogeneic HSCT offers little or no benefit for late infantile or early juvenile MLD. Given the variable outcomes, risks associated with myeloablative conditioning, and lack of demonstrated effectiveness in these subgroups, HSCT should not be considered an effective alternative to gene therapy for late infantile or early juvenile MLD.

Billing and Diagnosis Codes; Dose Ranges

HCPCS CodesHCPCS

C9399	Unclassified drugs or biologicals.
J3391	Injection, atidarsagene autotemcel, per treatment.
J3490	Unclassified drugs.
J3590	Unclassified biologics

ICD-10 Diagnosis CodesICD-10

E75.25

Metachromatic leukodystrophy

Recommended CD34+ cells/kg dose ranges by subgroup

Pre-symptomatic late infantile4.2–30 × 10^6 CD34+ cells/kg

Pre-symptomatic early juvenile9–30 × 10^6 CD34+ cells/kg

Early symptomatic early juvenile6.6–30 × 10^6 CD34+ cells/kg

Prior Authorization, Submission and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for both outpatient and inpatient services described in this policy. Providers must submit initial authorization requests via Authorization Manager and complete the Lenmeldy (atidarsagene autotemcel) prior authorization form (Policy 109). Out‑of‑network requests should be faxed to 888‑973‑0726.

Use Authorization Manager to submit initial authorization requests and clinical documentation.
Complete the Lenmeldy prior authorization form (109) in Authorization Manager.
Out‑of‑network providers: fax requests to 888-973-0726.

Denial Risk

Coverage Limited to Trial‑Defined Populations

Coverage is limited to the patient populations enrolled in the pivotal clinical trials and defined in the medical necessity criteria: pre-symptomatic late infantile, pre-symptomatic early juvenile, and early symptomatic early juvenile MLD meeting the specified genetic, biochemical, and clinical entry criteria. Patients who do not match the trial‑enrolled population characteristics are at risk for denial.

Clinical Background

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by deficient arylsulfatase A (ARSA) activity leading to sulfatide accumulation and progressive demyelination. Clinical subtypes are defined by age of onset and symptom status; the policy addresses treatment with atidarsagene autotemcel for the trial‑matched groups of pre‑symptomatic late infantile, pre‑symptomatic early juvenile, and early symptomatic early juvenile MLD. Allogeneic HSCT has historically been used but shows mixed outcomes and has not demonstrated effectiveness for the late infantile or early juvenile forms.

Key Definitions and Abbreviations

atidarsagene autotemcel / Lenmeldy — description and safety risks

Therapy identityAtidarsagene autotemcel (Lenmeldy) — an autologous CD34+ hematopoietic stem cell–based lentiviral vector gene therapy

MechanismAdds functional ARSA gene copies to autologous HSCs via Lenti‑D lentiviral transduction of CD34+ cells, which are reinfused to engraft and express ARSA in CNS and peripheral tissues

Key safety risksPotential for lentiviral vector–mediated insertional oncogenesis and development of hematologic malignancies; requires lifelong monitoring including annual CBC and integration site analysis as warranted for ≥15 years

GMFC-MLD definition used in eligibility

Definition (GMFC-MLD)Gross Motor Function Classification for MLD — used to classify gross motor status; Level 0 with ataxia or Level 1 correspond to walking independently for early symptomatic early juvenile eligibility