ModifiedUnitedHealthcarePolicy 2025D0079K

Zolgensma® (Onasemnogene Abeparvovec-Xioi) – Commercial Medical Benefit Drug Policyopen_in_new

Defines UnitedHealthcare commercial medical benefit coverage criteria, exclusions, coding, and use instructions for Zolgensma (onasemnogene abeparvovec-xioi), including one treatment per lifetime for eligible pediatric patients <2 years with SMA and specified genetic/clinical criteria. Also includes background, evidence summary, and applicable codes.

Policy Summary

PayerUnitedHealthcare

PolicyZolgensma® (Onasemnogene Abeparvovec-Xioi) – Commercial Medical Benefit Drug Policyopen_in_new

Policy CodePolicy 2025D0079K

Change TypeRevised coverage criteria; inpatient admission restriction added

Effective DateDec 1, 2025

Next Review Date

Key ActionSubmit medical records confirming SMN1 biallelic mutation/deletion and either symptomatic diagnosis by an SMA neurologist or newborn screening plus SMN2 copy number (<=4).

SourceLink

POLICY UPDATE CHANGES

Revised coverage criteria; added criterion requiring the provider does not request a planned inpatient admission for the sole purpose of administering Zolgensma.

1Treatment courses allowed per lifetime

<2Maximum patient age for coverage

<=4SMN2 copies eligible for presymptomatic newborns

1:50

Coverage Summary

Defines UnitedHealthcare commercial medical benefit coverage for Zolgensma (onasemnogene abeparvovec-xioi) as a one treatment per lifetime indication for eligible pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) who meet specified genetic and clinical criteria. Coverage stance: covered_with_criteria. Effective date and last review: December 1, 2025.

Medically Necessary / Initial Therapy Criteria

Medically Necessary / Initial coverage criteria

Zolgensma is proven and medically necessary for one treatment per lifetime for the treatment of spinal muscular atrophy (SMA) in patients who meet ALL of the following criteria:

ALL of the following

ALL of the following
- ONE of
  - Homozygous gene deletion or mutation of survival motor neuron 1 (SMN1) gene (e.g., homozygous deletion of exon 7 at locus 5q13)
  - Compound heterozygous mutation of SMN1 gene (e.g., deletion of SMN1 exon 7 (allele 1) and mutation of SMN1 (allele 2))
ALL of the following
- ONE of
  - Diagnosis of symptomatic SMA by a neurologist with expertise in the diagnosis of SMA
  - ALL of the following
    Diagnosis of SMA based on the results of SMA newborn screening
    Submission of medical records confirming that patient has 4 copies or less of SMN2 gene<=4 copies
For use in a neonatal patient born prematurely, the full-term gestational age has been reached
Patient is less than 2 years of age<2 years
ALL of the following
- NEITHER of
  - Invasive ventilation or tracheostomy
  - Use of non-invasive ventilation beyond use for naps and nighttime sleep
Zolgensma is prescribed by a neurologist with expertise in the treatment of SMA
Patient is not to receive routine concomitant SMN modifying therapy (e.g., Evrysdi (risdiplam), Spinraza (nusinersen)); patient's medical record will be reviewed and any current authorizations for SMN modifying therapy will be terminated upon Zolgensma approval
Patient does not have an elevated anti-AAV9 antibody titer above 1:50<=1:50
Patient will receive prophylactic prednisolone (or glucocorticoid equivalent) prior to and following receipt of Zolgensma in accordance with the FDA approved Zolgensma labeling
Patient will receive Zolgensma intravenously in accordance with the FDA approved labelingIV route
Patient has never received Zolgensma treatment in the patient's lifetimeone lifetime
Provider does not request a planned inpatient admission for the sole purpose of administering Zolgensma
Authorization will be issued for no more than one treatment per lifetime and for no longer than 45 days from approval or until 2 years of age, whichever is first<=1 treatment; duration <=45 days or until age 2

Not Medically Necessary / Exclusions

Not medically necessary / Exclusions

Zolgensma is not proven or medically necessary for:

ANY of the following

The treatment of pre-symptomatic patients diagnosed by newborn screening who have more than 4 copies of the SMN2 gene>4 copies
The treatment of symptomatic later-onset SMA older than 2 years of age>=2 years
SMA without chromosome 5q mutations or deletions
The routine combination treatment of SMA with concomitant SMN modifying therapy

Provider Actions & Prior Authorization

Prior Authorization

Prior authorization required and limited duration

Authorization limited to one treatment per lifetime. Duration: no more than 45 days from approval or until patient is 2 years of age, whichever is first.

J3399

Documentation Required

Confirm genetic testing and provide records

Submit medical records confirming SMN1 biallelic mutation/deletion and either symptomatic diagnosis by an SMA neurologist or newborn screening plus SMN2 copy number (≤4).

Applicable Codes

HCPCS - drug administrationHCPCSCovered

J3399

Injection, Onasemnogene abeparvovec-xioi, per treatment, up to 5x10^15 vector genomes

ICD-10 diagnosis codes (reference)ICD-10

G12.0	Infantile spinal muscular atrophy, type I [Werdnig-Hoffmann]
G12.1	Other inherited spinal muscular atrophy
G12.8	Other SMAs and related syndromes
G12.9	Spinal muscular atrophy, unspecified

Clinical Evidence Summary

All patients alive and free of ventilatory support at median follow-up; high rates of motor milestonesSPR1NT presymptomatic outcomes

Clinical trials (phase 1 and phase 3 cohorts) showed marked improvements in survival and motor milestones after a one-time IV administration of Zolgensma, but safety signals include elevated liver enzymes (serum aminotransferases) that were attenuated by prednisolone, the need for planned corticosteroid (steroid) management, and specific safety concerns with intrathecal administration in older patients (FDA partial hold related to preclinical dorsal root ganglia findings). For premature neonates, infusion is delayed until the infant reaches full-term gestational age because concomitant corticosteroid treatment may adversely affect neurological development.

Background

Zolgensma is a one-time intravenous SMN1 gene replacement therapy that delivers a functional copy of the human SMN gene via an AAV9 vector to treat the root cause of SMA caused by bi-allelic SMN1 mutations or deletions. It is administered as a single IV dose designed to provide sustained SMN protein expression in non-dividing motor neurons. Use in premature neonates is not recommended until full-term gestational age because concomitant corticosteroid therapy may adversely affect neurological development; infusion should be delayed until full-term gestational age is reached.

SMN1 biallelic mutation/deletion: Homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene on chromosome 5q (e.g., homozygous deletion of exon 7) or compound heterozygous mutations is required for diagnosis and eligibility.

SMN2 copy number: The number of SMN2 gene copies is used as a predictor of SMA phenotype and eligibility; presymptomatic newborns with more than 4 copies of SMN2 are excluded from treatment per policy considerations.

Anti-AAV9 antibody titer: A serologic measure of antibodies to AAV9; levels above 1:50 are exclusionary for Zolgensma under this policy.

Revision History

2025-12-01revisedLatest

Revised coverage criteria: added criterion that provider does not request a planned inpatient admission for the sole purpose of administering Zolgensma; supporting information updated (Background, Clinical Evidence, References); previous policy version 2024D0079J archived.