Background
Lenmeldy is a one-time gene therapy developed to treat children with pre-symptomatic late infantile, pre-symptomatic early juvenile and early symptomatic early juvenile, referred to as early-onset, metachromatic leukodystrophy (MLD). MLD is caused by a defect in the arylsulfatase A (ARSA) gene, which causes the body to produce reduced or no ARSA enzyme. LENMELDY is made specifically for each child, using the child’s own blood stem cells, and adding functional copies of the ARSA gene to their cells. This may allow you to produce sufficient ARSA enzyme to stop or slow the progression of MLD symptoms.

Policy:   
Lenmeldy is considered MEDICALLY NECESSARY when the following criteria are met:

1.  Patient meets ONE of the following (i, ii, or iii):
   1. Patient has presymptomatic late infantile (PSLI) metachromatic leukodystrophy (MLD) and meets ALL of the following (a, b, and c):
      1. Patient has an arylsulfatase A (ARSA) genotype consistent with presymptomatic late infantile MLD [documentation required]; AND
      2. The disease onset was at ≤ 30 months of age; AND
      3. According to the prescribing physician, the patient is presymptomatic; OR

Note: Presymptomatic status is defined as the absence of neurological signs and symptoms of MLD. However, presymptomatic children are allowed to have abnormal reflexes or abnormalities on brain magnetic resonance imaging and/or nerve conduction tests not associated with functional impairment (e.g., no tremor, no peripheral ataxia).

1. Patient has presymptomatic early juvenile (PSEJ) metachromatic leukodystrophy (MLD) and meets ALL of the following (a, b, and c):
   1. Patient has an arylsulfatase A (ARSA) genotype consistent with presymptomatic early juvenile MLD [documentation required]; AND
   2. The disease onset was between > 30 months and < 7 years of age; AND
   3. According to the prescribing physician, the patient is presymptomatic; OR

Note: Presymptomatic status is defined as the absence of neurological signs and symptoms of MLD or physical examination findings limited to abnormal reflexes and/or clonus. However, presymptomatic children were allowed to have abnormal reflexes or abnormalities on brain magnetic resonance imaging and/or nerve conduction tests not associated with functional impairment (e.g., no tremor, no peripheral ataxia).

1. Patient has early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD) and meets ALL of the following (a, b, and c):
   1. Patient has an arylsulfatase A (ARSA) genotype consistent with early symptomatic early juvenile MLD [documentation required]; AND
   2. The disease onset was between > 30 months and < 7 years of age; AND
   3. The patient has early symptomatic status by meeting BOTH of the following [(1) and (2)]:
      1. Patient is walking independently as defined as being at gross motor function classification for metachromatic leukodystrophy [GMFC-MLD] Level 0 (with or without ataxia) or GMFC-MLD Level 1; AND
      2. Patient has an intelligence quotient ≥ 85;

2. Patients have not received Lenmeldy in the past
3. Patients have low arylsulfatase A (ARSA) activity indicative of metachromatic leukodystrophy (MLD)

Note: Normal laboratory reference range for ARSA activity in the peripheral blood mononuclear cells is 31 to 198 nmol/mg/hour. In patients with MLD, ARSA activity is 0% to less than or equal to 13%.

4. Patient has elevated sulfatide levels above the normal laboratory reference range as evaluated by 24-hour urine collection
5. A hematopoietic stem cell transplantation is appropriate for the patient
6. Patient will have discontinued from antiretrovirals (prophylactic for human immunodeficiency virus) for at least 1 month prior to mobilization
7. Patient screening is negative for ALL of the following (i, ii, iii, iv, v, and vi):
   1. Human immunodeficiency virus (HIV)-1 and HIV-2 [documentation required]; AND
   2. Hepatitis B virus [documentation required]; AND
   3. Hepatitis C virus [documentation required]; AND
   4. Human T-lymphotrophic virus (HTLV)-1 and HTLV-2 [documentation required]; AND
   5. Cytomegalovirus [documentation required]; AND
   6. Mycoplasma [documentation required]; AND
8. The medication is prescribed by a hematologist, a neurologist, a medical geneticist physician, or a stem cell transplant specialist physician

Dosing: The recommended dose of Lenmeldy is one dose given by intravenous infusion to provide a one-time (per lifetime) single dose as outlined below.

I. For presymptomatic late infantile MLD, the minimum recommended dose is 4.2 x 10⁶ CD34+ cells/kg of body weight up to a maximum recommended dose of 30 x 10⁶ CD34+ cells/kg of body weight [verification required]; OR

II. Presymptomatic early juvenile MLD, the minimum recommended dose is 9 x 10⁶ CD34+ cells/kg of body weight up to a maximum recommended dose of 30 x 10⁶ CD34+ cells/kg of body weight [verification required]; OR

III. Early symptomatic early juvenile MLD, the minimum recommended dose is 6.6 x 10⁶ CD34+ cells/kg of body weight up to a maximum recommended dose of 30 x 10⁶ CD34+ cells/kg of body weight [verification required].

Administration

I. Patient should undergo mobilization, apheresis, and myeloablative conditioning

II. A granulocyte-colony stimulating factor product with or without a hematopoietic stem cell mobilizer should be utilized for mobilization

III. Busulfan should be used for myeloablative conditioning

References

1. Lenmeldy™ intravenous infusion [prescribing information]. Boston, MA: Orchard; March 2024.
2. Lenmeldy™ intravenous infusion {billing and coding guide]. Boston, MA: Orchard; April 2024.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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