CurrentCignaPolicy IP0695

Lenmeldy (atidarsagene autotemcel) gene therapy for metachromatic leukodystrophy (MLD)

Cigna coverage policy for one-time, per-lifetime intravenous infusion of Lenmeldy for treatment of specific pediatric MLD subtypes; applies to benefit plans administered by Cigna Companies and requires prior authorization and documentation.

Policy Summary

PayerCigna

PolicyLenmeldy (atidarsagene autotemcel) gene therapy for metachromatic leukodystrophy (MLD)

Policy CodePolicy IP0695

Change TypeCoding and clinical criteria updates (2024–2025)

Effective Date08/15/2024

Next Review Date

Key ActionSubmit prior authorization with documentation of ARSA genotype and activity, 24-hour urine sulfatide levels, infectious disease screening, current body weight (within 30 days), and verification of no prior Lenmeldy or recent allogeneic transplant.

SourceLink

POLICY UPDATE CHANGES

New policy created (Coverage Policy Number IP0695).

Added HCPCS code J3391 effective 7/1/2025 and updated J3590 description (code effective until 6/30/2025).

Added requirement that prescribing physician confirm patient discontinued antiretrovirals for at least 1 month prior to mobilization.

Clarified screening criterion wording to 'Patient screening is negative for ALL of the following...' and removed qualifier 'Prior to collection of cells for manufacturing'.

Dosing language revised to add 'of body weight' after cells/kg and 'Current patient body weight has been obtained within the past 30 days'.

one-timeNumber of doses approved

IP0695Coverage Policy Number

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

FDA-Approved Indication and Criteria

FDA-Approved Indication - Approval Criteria

Approve one-time (per lifetime) single dose when ALL of the following A through K are met:

ALL of the following

A) Disease subtype
- i. Presymptomatic late infantile (PSLI)
  - Patient has an ARSA genotype consistent with presymptomatic late infantile MLD
    [documentation required]
  - Disease onset was at ≤ 30 months of age
  - According to prescribing physician, patient is presymptomatic
    Presymptomatic = absence of neurological signs and symptoms; abnormal reflexes or MRI/nerve conduction abnormalities allowed if not associated with functional impairment
- ii. Presymptomatic early juvenile (PSEJ)
  - Patient has an ARSA genotype consistent with presymptomatic early juvenile MLD
    [documentation required]
  - Disease onset between > 30 months and < 7 years of age
  - According to prescribing physician, patient is presymptomatic
    Presymptomatic = absence of neurological signs/symptoms or physical exam findings limited to abnormal reflexes and/or clonus; MRI/nerve conduction abnormalities allowed if not associated with functional impairment
- iii. Early symptomatic early juvenile (ESEJ)
  - Patient has an ARSA genotype consistent with early symptomatic early juvenile MLD
    [documentation required]
  - Disease onset between > 30 months and < 7 years of age
  - c) Early symptomatic status (both required)
    Patient is walking independently defined as GMFC-MLD Level 0 (with or without ataxia) or Level 1
    Patient has an intelligence quotient (IQ) ≥ 85
B) Patient has not received Lenmeldy in the past
[verification in claims history required; if claims unavailable, prescribing physician confirmation acceptable]
C) Patient has low ARSA activity indicative of MLD
[documentation required]; normal peripheral blood mononuclear cell ARSA reference range 31–198 nmol/mg/hour; MLD typically 0% to ≤13% activity
D) Patient has elevated sulfatide levels above normal laboratory reference range by 24-hour urine collection
[documentation required]
E) According to prescribing physician, hematopoietic stem cell transplantation is appropriate for the patient
F) According to prescribing physician, patient will have discontinued antiretrovirals (HIV prophylactic agents) for at least 1 month prior to mobilization
Examples: abacavir, emtricitabine, lamivudine, zidovudine; [documentation required]
G) Mobilization and conditioning plan
- Patient will undergo mobilization, apheresis, and myeloablative conditioning
- A granulocyte-colony stimulating factor product with or without a hematopoietic stem cell mobilizer will be utilized for mobilization
  Examples: filgrastim products; Mozobil (plerixafor)
- Busulfan will be used for myeloablative conditioning
H) Infectious disease screening negative
- Patient screening negative for HIV-1 and HIV-2
  [documentation required]
- Patient screening negative for Hepatitis B
  [documentation required]
- Patient screening negative for Hepatitis C
  [documentation required]
- Patient screening negative for HTLV-1 and HTLV-2
  [documentation required]
- Patient screening negative for Cytomegalovirus
  [documentation required]
I) Prescribed by a specialist: hematologist, neurologist, medical geneticist, or stem cell transplant specialist
J) Current patient body weight has been obtained within the past 30 days
[documentation required]
K) Dosing ranges by MLD subtype (select ONE)
- For presymptomatic late infantile MLD: minimum recommended dose 4.2 x 10^6 CD34+ cells/kg of body weight up to maximum 30 x 10^6 CD34+ cells/kg
  [verification required]
- For presymptomatic early juvenile MLD: minimum recommended dose 9 x 10^6 CD34+ cells/kg of body weight up to maximum 30 x 10^6 CD34+ cells/kg
  [verification required]
- For early symptomatic early juvenile MLD: minimum recommended dose 6.6 x 10^6 CD34+ cells/kg of body weight up to maximum 30 x 10^6 CD34+ cells/kg
  [verification required]

Policy statement: Prior authorization required; approvals are one-time (per lifetime) and issued for 1 year to allow preparation and administration

See documentation and verification requirements in policy

Conditions Not Covered / Not Medically Necessary

Lenmeldy is considered not medically necessary for the following conditions (non-exhaustive):

ANY of the following

Late juvenile form of metachromatic leukodystrophy (safety/efficacy not established)
Adult form of metachromatic leukodystrophy (safety/efficacy not established)
GMFC-MLD greater than Level 1 (patients with GMFC-MLD >1 were not included in clinical studies)
Prior allogeneic hematopoietic stem cell transplantation in the past 6 months or evidence of residual donor cells
Prescribing physician must confirm no prior allogeneic transplant within past 6 months
Prior receipt of gene therapy

Relevant Billing Codes

Covered HCPCS (when criteria met)HCPCSCovered

J3391	Injection, atidarsagene autotemcel, per treatment (Code Effective 7/1/2025)
J3590	Unclassified biologics (Code Effective Until 6/30/2025)

Covered HCPCS - notesmixed

J3391	Code Effective 7/1/2025
J3590	Code Effective Until 6/30/2025

Prior Authorization, Documentation, and Billing Rules

Prior Authorization

Prior authorization required

Prior Authorization is required for coverage of Lenmeldy. All approvals are provided as a one-time (per lifetime) single dose and the approval duration is 1 year to allow preparation and administration.

Affected HCPCS codes: J3391; J3590

Documentation Required

Required documentation and verification

Providers must supply documentation for ARSA genotype and ARSA activity results, 24-hour urine sulfatide levels, infectious disease screening, current patient body weight (obtained within the past 30 days), and verification that the patient has not previously received Lenmeldy or had a recent allogeneic transplant as specified in the criteria.

ARSA genotype (documentation required)
ARSA activity results (documentation required; normal PBMC range 31–198 nmol/mg/hour; MLD typically 0% to ≤13%)

Key Thresholds and Clinical Requirements

Thresholds and Requirements

ARSA activity rangeTypically 0% to <= 13% in patients with MLD; normal PBMC reference range 31–198 nmol/mg/hour

IQ requirement for ESEJ>= 85

GMFC-MLD allowed levels for ESEJLevel 0 or Level 1 (walking independently)

Minimum dosing by subtypePSLI 4.2 x 10^6 CD34+ cells/kg; PSEJ 9 x 10^6 CD34+ cells/kg; ESEJ 6.6 x 10^6 CD34+ cells/kg

Maximum dosing (all subtypes)30 x 10^6 CD34+ cells/kg

Antiretroviral discontinuation prior to mobilization>= 1 month

Body weight documentation window

Clinical Background

Lenmeldy (atidarsagene autotemcel) is an autologous hematopoietic stem cell (HSC)-based lentiviral gene therapy that delivers functional copies of the ARSA gene to treat certain pediatric forms of metachromatic leukodystrophy (MLD). The therapy is manufactured ex vivo from the patient’s own HSCs collected by mobilization and apheresis; manufacturing typically takes about 5–6 weeks. Prior to infusion, patients undergo myeloablative conditioning with busulfan, with a minimum washout of 24 hours between completion of conditioning and infusion. Lenmeldy is administered as a single intravenous infusion given one time per lifetime. [[3]]

Clinical development included two single-arm, open-label trials and an expanded access program enrolling a total of 39 children: 20 with presymptomatic late infantile (PSLI), 7 with presymptomatic early juvenile (PSEJ), and 10 with early symptomatic early juvenile (ESEJ) MLD. Patients were required to have biochemical and molecular confirmation of MLD, including reduced ARSA activity below the normal PBMC reference range and two disease-causing ARSA alleles; selected patients also had 24-hour urine collections demonstrating elevated sulfatide levels. Primary efficacy assessments focused on motor and neurocognitive outcomes using the GMFC-MLD scale and age-appropriate cognitive testing, with comparisons to an external natural history cohort. [[5]]

Trials demonstrated that, with follow-up of roughly 6.7 years, treatment with Lenmeldy was associated with a substantially lower risk of severe motor impairment (GMFC-MLD level ≥ 5) or death and higher rates of survival without severe cognitive impairment versus untreated natural history controls in the enrolled PSLI, PSEJ, and ESEJ populations. The GMFC-MLD scale ranges from Level 0 (normal walking) to Level 6 (loss of all gross motor function) and was used to define allowed functional status in eligibility (e.g., ESEJ patients must be GMFC-MLD Level 0 or 1). [[6]][[5]]

Dosing is weight-based and varies by MLD subtype. The policy references minimum recommended dose thresholds of 4.2 x 10^6 CD34+ cells/kg for PSLI, 9 x 10^6 CD34+ cells/kg for PSEJ, and 6.6 x 10^6 CD34+ cells/kg for ESEJ, with a common maximum of 30 x 10^6 CD34+ cells/kg for all subtypes; verification of appropriate weight-based dosing is required. The treatment pathway therefore includes mobilization (granulocyte‑colony stimulating factor with or without a mobilizer such as plerixafor), apheresis, manufacturing, myeloablative conditioning with busulfan, and the single intravenous infusion of the manufactured, transduced HSC product. [[3]][[13]][[11]]

Defined Terms

Definitions

PresymptomaticAbsence of neurological signs and symptoms of MLD; presymptomatic children may have abnormal reflexes or imaging/nerve conduction abnormalities not associated with functional impairment (definition varies slightly by subtype in policy).

GMFC-MLDGross Motor Function Classification for Metachromatic Leukodystrophy; scale Level 0 (normal) to Level 6 (loss of all gross motor function).

Early symptomatic (ESEJ) - walking definitionWalking independently defined as GMFC-MLD Level 0 (with or without ataxia) or Level 1.

Policy Changes and History

08/15/2024policy_created

Initial policy established (Coverage Policy Number IP0695) as a new coverage policy for Lenmeldy.

05/15/2025coding_update

Updated HCPCS coding: added J3391 (effective 7/1/2025) and updated J3590 description noting code effective until 6/30/2025.

06/05/2025clinical_criteria_revisionLatest

Annual revision added requirement that prescribing physician confirm antiretrovirals were discontinued for at least 1 month prior to mobilization, clarified infectious screening wording to 'Patient screening is negative for ALL of the following...', removed prior qualifier about collection timing, and revised dosing language to add 'of body weight' and require current body weight obtained within the past 30 days.