UnitedHealthcare Zolgensma Coverage Update

Coverage Criteria for Zolgensma (IV onasemnogene abeparvovec)

Initial therapy (IV Zolgensma)

Covered when ALL of the following are met:

Genetic confirmation: Submission of medical records confirming mutation or deletion of SMN1 resulting in either homozygous deletion/mutation (e.g., exon 7) or compound heterozygous SMN1 mutation

Diagnosis evidence: Either: diagnosis of symptomatic SMA by a neurologist with expertise in SMA; OR diagnosis based on SMA newborn screening plus medical records confirming four or fewer SMN2 copies

Age and gestational status: Patient is less than 2 years of age; if born premature, full-term gestational age has been reached< 2 years

Respiratory status: Patient is not dependent on invasive ventilation or tracheostomy and not dependent on non-invasive ventilation beyond naps/nighttime sleep

Provider and administration: Zolgensma is prescribed by a neurologist with expertise in SMA and will be administered intravenously per FDA labeling; prophylactic prednisolone (or equivalent) will be given prior to and following infusion per FDA labeling

Concomitant therapy and prior treatment: Patient is not to receive routine concomitant SMN modifying therapy (e.g., risdiplam, nusinersen); patient has never received Zolgensma previously

Immunologic criteria: Anti-AAV9 antibody titer is not elevated above 1:50<= 1:50

Authorization limits: Authorization is limited to one treatment per lifetime and issued for no more than 45 days from approval or until patient reaches 2 years of age, whichever is firstone lifetime; <=45 days

Coverage criteria — general

Covered when ALL of the following are met:

FDA indication: Pediatric patients less than 2 years of age with bi-allelic SMN1 mutations (per FDA labeling)age <2 years

Center and monitoring requirements: Treatment must be performed at centers with SMA expertise, trained personnel, ability to monitor and manage gene therapy side effects, and systematic data collection/registry use is recommended

Presymptomatic treatment decision: In presymptomatic patients, treatment decisions should be based primarily on SMN2 copy number: immediate treatment recommended for up to 4 copies; watchful waiting may be considered for higher copy numbers; SMN2 copy number testing should be performed in an expert laboratorySMN2 copy number per laboratory result

For pre-symptomatic patients identified by newborn screening, treatment decisions should be guided primarily by SMN2 copy number. Current expert guidance recommends immediate treatment for patients with up to 4 copies and consideration of watchful waiting for higher copy numbers; therefore, Zolgensma is not considered proven or medically necessary for pre-symptomatic patients with more than 4 SMN2 copies. Coverage requires documented genetic confirmation of SMA (bi-allelic SMN1 mutation/deletion) and, when relied upon, laboratory-confirmed SMN2 copy number performed in an experienced laboratory.

For symptomatic patients, coverage is limited to those meeting the age and clinical criteria (patient <2 years of age at time of infusion and meeting respiratory and clinical status requirements). Use of Zolgensma for symptomatic later-onset SMA in patients older than 2 years is not supported by this policy and is considered not medically necessary except as described by explicit criteria or investigational protocols.

Zolgensma has not been evaluated for use in patients with advanced SMA (for example, complete paralysis of limbs or permanent ventilator dependence), and such use is specifically listed as a limitation of use. The safety and effectiveness of repeat administration of Zolgensma have also not been evaluated; repeat dosing is not supported by current evidence and may trigger non-coverage review.

Expert consensus emphasizes that centers administering gene replacement therapy should have broad SMA expertise, trained personnel, and capacity for long-term outcome monitoring and registry participation. For heavier patients (see consensus guidance regarding weight thresholds), alternative disease-modifying therapies or carefully designed protocols should be considered.

Additional exclusions and nuances include: Zolgensma is not proven or medically necessary for SMA that is not caused by chromosome 5q SMN1 mutations/deletions, and routine combination treatment with concomitant SMN-modifying therapies is not supported.

For presymptomatic infants with >4 SMN2 copies, treatment is not recommended by this policy; centers should follow expert recommendations and newborn screening guidance when making individualized decisions. For symptomatic later-onset patients older than 2 years, treatment is considered not medically necessary under this policy.

The policy further notes that for patients above specified weight considerations and for those with advanced disease, use should be limited to specific circumstances or clinical protocols given the lack of safety and effectiveness data for repeat administration and advanced-stage treatment.

Repeat administration of Zolgensma is not supported by available evidence; the safety and effectiveness of administering additional doses have not been evaluated and therefore repeat dosing is not authorized by this policy.

Use of Zolgensma in patients with advanced SMA (for example, complete limb paralysis or permanent ventilator dependence) has also not been evaluated and is considered a limited use that requires careful specialist review or would be managed only in the context of a specific protocol or investigational setting.

Coding and Billing Information

Procedure/Billing CodesHCPCS

J3399

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

Diagnosis CodesICD-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

Coding referencesmixed

NDC/HCPCS/CPT

Not specified in this portion of the document; package insert referenced (Zolgensma [package insert], July 2024).

inv-10: Anti-AAV9 antibody titer

Maximum allowable anti-AAV9 antibody titerAnti-AAV9 antibody titer must be less than or equal to 1:50 for eligibility

inv-11: Weight threshold for IV therapy

Weight threshold for IV administrationIV Zolgensma data and expert consensus support caution for patients > 13.5 kg; patients above this weight should be considered for alternative therapies or treated only under specific circumstances or rigorous protocols

Provider Requirements, Documentation, and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Zolgensma (onasemnogene abeparvovec-xioi). Authorization is limited to one lifetime treatment and will be issued for no more than 45 days from approval or until the patient reaches 2 years of age, whichever occurs first.

One lifetime treatment per patient.
Authorization duration: up to 45 days from approval or until age 2, whichever is first.
Requests must include prior authorization submitted before treatment.

Denial Risk

Conditions That Will Lead to Denial

Requests will be denied when the patient does not meet the policy clinical eligibility or falls into exclusion scenarios.

Patient is older than 2 years of age at time of treatment.

Background

Zolgensma (onasemnogene abeparvovec-xioi) is a one-time intravenous, adeno-associated virus serotype 9 (AAV9) mediated gene replacement therapy that delivers a functional copy of the SMN1 gene to address the underlying genetic defect in spinal muscular atrophy (SMA). It is intended to provide durable SMN protein expression following a single IV infusion and is administered per FDA labeling at specialized centers with appropriate expertise and monitoring capability.

Definitions and Outcome Measures

inv-21: Genetic confirmation of SMA

DefinitionGenetic confirmation of SMA requires documentation of SMN1 gene alteration such as homozygous deletion or mutation (e.g., homozygous deletion of exon 7 at locus 5q13) or compound heterozygous SMN1 mutations (e.g., deletion of exon 7 on one allele and mutation on the other)

inv-22: SMN2 copy number

DefinitionSMN2 copy number is the number of SMN2 gene copies and is the strongest genetic predictor of SMA clinical phenotype

Clinical implicationHigher SMN2 copy number generally predicts less severe SMA phenotypes (e.g., four or more copies are associated with non-type I presentations)

inv-23: SMN2 copy number

Testing guidance in presymptomatic patients

Policy Revision History

2025-09-01policy_effective_dateLatest

Policy effective 09/01/2025; instruction added to refer to North Carolina Medicaid clinical policy and previous policy version CS2025D0079Q archived.

2025-09-01status_updateLatest

Policy status set to MODIFIED with effective date 09/01/2025; authorization limits reiterated (one lifetime treatment, age and clinical restrictions).

OpenPayer

Zolgensma (Onasemnogene abeparvovec-xioi) coverage