ModifiedColorado Rocky Mountain Health PlansPolicy IEXD0079.10

Zolgensma (Onasemnogene abeparvovec-xioi) — Medical Benefit Drug Coverage Criteria

Policy governs medical benefit drug coverage criteria for a one-time intravenous gene replacement therapy (Zolgensma) for spinal muscular atrophy (SMA) under UnitedHealthcare Individual Exchange plans in most states; affects prescribers, treating neurologists, and prior authorization reviewers.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyZolgensma (Onasemnogene abeparvovec-xioi) — Coverage Criteria

Policy CodePolicy IEXD0079.10

Change TypeRevised coverage criteria (materials and non-material updates)

Effective DateDecember 1, 2025

Next Review Date

Key ActionSubmit prior authorization with medical records confirming SMN1 mutation/deletion, SMN2 copy number, and documentation that no planned inpatient admission is requested solely to administer Zolgensma.

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.

Updated Background, Clinical Evidence, and References sections to reflect the most current information.

onetreatment per lifetime authorized when criteria met

<2ymaximum age for covered administration

≤1:50required anti-AAV9 titer

J3399procedure code

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Coverage Criteria

Initial Therapy

Covered when ALL of the following are met:

Initial IV Zolgensma coverage: 1) Submission of medical records confirming biallelic SMN1 mutation or deletion (e.g., homozygous deletion of exon 7 at 5q13 or compound heterozygous mutation).

Diagnostic criteria: 2) One of the following: a) Diagnosis of symptomatic SMA by a neurologist with expertise in SMA; OR b) Diagnosis of SMA by newborn screening plus documentation that the patient has four or fewer copies of SMN2.

Neonatal/age requirements: 3) For neonatal patients born prematurely, full-term gestational age has been reached; and 4) Patient is less than 2 years of age at time of administration.

Respiratory status: 5) Patient is not dependent on invasive ventilation (including tracheostomy) and does not require non-invasive ventilation other than for naps and nighttime sleep.

Prescriber qualifications: 6) Zolgensma is prescribed by a neurologist with expertise in the treatment of SMA.

Concomitant therapy: 7) Patient will not receive routine concomitant SMN‑modifying therapy (e.g., risdiplam, nusinersen); existing authorizations for such therapies will be terminated upon Zolgensma approval.

Antibody and steroid requirements: 8) Anti‑AAV9 antibody titer is not elevated above 1:50; and 9) Patient will receive prophylactic prednisolone (or glucocorticoid equivalent) prior to and following Zolgensma per FDA labeling.

Route and prior exposure: 10) Zolgensma will be administered intravenously in accordance with FDA approved labeling; and 11) Patient has never previously received Zolgensma (one treatment per lifetime).

Operational limits: 12) Provider does not request a planned inpatient admission solely for the purpose of administering Zolgensma; and 13) Authorization will be limited to one treatment per lifetime and for no longer than 45 days from approval or until the patient reaches 2 years of age, whichever is first.

General coverage considerations

Covered when criteria in the payer's revised coverage rationale are met and aligned with FDA indication and expert consensus considerations:

Primary coverage conditions: Patient is a pediatric patient less than 2 years of age with bi‑allelic SMN1 mutations consistent with the FDA indication, and provider meets payer documentation and authorization requirements; provider does not request a planned inpatient admission solely to administer Zolgensma.

Presymptomatic evaluation: Presymptomatic patients identified by newborn screening should be evaluated urgently; treatment decisions for presymptomatic patients should be primarily based on SMN2 copy number determined in an expert laboratory.SMN2 copy number determination required

Older/heavier patient considerations: For older or heavier patients, exercise caution: limited efficacy and safety data exist for older/heavier patients and risk increases with dose proportional to weight; consider alternatives and discuss risk‑benefit and expectations with families; IV therapy for patients >21 kg is not recommended outside rigorous protocols.

Exclusions include treatment of pre-symptomatic patients identified by newborn screening who have more than four copies of the SMN2 gene, treatment of symptomatic later-onset SMA in patients older than 2 years, SMA that does not involve chromosome 5q SMN1 mutations or deletions, and routine combination treatment with concomitant SMN modifying therapies. These situations are considered not proven or not medically necessary for Zolgensma.

Use of intravenous gene replacement therapy in patients with advanced or atypical presentations of SMA has limited evidence. The 2024 European expert consensus advises caution for heavier and older patients because dose (and therefore risk) increases with weight and age, and available data in these populations are scarce. Combination use of gene therapy with other disease‑modifying treatments is not recommended outside controlled clinical trials; evidence does not currently support routine combinatorial therapy.

Additionally, the safety and effectiveness of repeat administration have not been evaluated, and the use of Zolgensma in patients with advanced SMA (for example, complete limb paralysis or permanent ventilator dependence) has not been evaluated, which further limits support for use in these populations.

Presymptomatic patients identified by newborn screening should have urgent evaluation of SMN2 copy number to guide treatment: patients with more than four SMN2 copies are not considered appropriate candidates for Zolgensma under this policy. Symptomatic, later‑onset SMA in patients older than 2 years is not supported. For older or heavier patients, the European consensus emphasizes very cautious consideration because of limited data and dose-related risks; intrathecal approaches or alternative treatments may be considered where evidence or protocols exist.

The policy also specifies that Zolgensma is indicated only for patients with documented bi-allelic SMN1 mutations/deletions and that routine combination with other SMN‑modifying therapies is not recommended.

Repeat administration of Zolgensma is not supported by available evidence. The policy notes that the safety and effectiveness of repeat dosing have not been evaluated, and therefore repeat administration is considered not proven and is not covered.

Coding and Eligibility Parameters

Applicable CPT/HCPCS CodesHCPCS

J3399

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

Applicable 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

inv-09: Anti-AAV9 antibody titer — required maximum titer for eligibility

Required maximum titerAnti-AAV9 antibody titer ≤ 1:50

Test timingMeasured prior to administration as part of eligibility assessment

Trigger for denialRequests will be denied if anti-AAV9 antibody titer is above 1:50

inv-10: Age at administration — maximum age limit for covered administration

Maximum age for covered administrationPatient must be less than 2 years of age at time of administration

Authorization duration linkageAuthorization valid for no longer than 45 days from approval or until patient reaches 2 years of age, whichever is first

Provider Actions and Authorization Requirements

Prior Authorization

Prior authorization aligns with coverage criteria and FDA indication

Prior authorization is required and decisions will align with the coverage criteria and the FDA-approved indication for Zolgensma (onasemnogene abeparvovec-xioi). Reviewers will confirm that requests meet all policy coverage criteria (including age, genetic confirmation, and not previously treated with Zolgensma) and that administration will follow FDA labeling.

Prior authorization required prior to administration
Authorization issued for a single lifetime treatment and limited in duration (no longer than 45 days from approval or until 2 years of age, whichever is first)

Prior Authorization

Planned inpatient admission for administration

Do not approve requests that include a planned inpatient admission solely for the purpose of administering Zolgensma. Zolgensma should be administered intravenously per FDA labeling in the appropriate clinical setting; routine inpatient admission for administration alone is not supported by this policy.

Requests that list planned inpatient admission only for Zolgensma administration will be denied or returned for correction

Background

Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder caused primarily by biallelic SMN1 variants leading to degeneration of motor neurons. Zolgensma (onasemnogene abeparvovec‑xioi) is a one‑time AAV9‑mediated SMN1 gene replacement therapy intended to provide sustained SMN protein expression when administered per labeled IV indications. Expert consensus emphasizes early initiation of disease‑modifying therapy—ideally in the presymptomatic stage—because earlier treatment is associated with markedly better outcomes; conversely, evidence is limited for older, heavier, or advanced‑disease patients, and repeat dosing or combination therapy lacks supportive data.

Definitions

inv-20: SMN1 mutation/deletion — definition and examples

DefinitionBiallelic (homozygous) deletion or compound heterozygous mutation of the SMN1 gene (e.g., homozygous deletion of exon 7 at locus 5q13 or deletion of exon 7 on one allele with a mutation on the other)

Documentation requiredSubmission of medical records confirming SMN1 mutation or deletion (e.g., chart notes, laboratory values) is required for coverage

Exclusion implicationSMA without chromosome 5q SMN1 mutations/deletions is not eligible under this policy

inv-21: SMN2 copy number — role in phenotype and treatment considerations

Role in phenotypeNumber of SMN2 copies correlates with SMA severity and is the best predictor of clinical phenotype

Clinical use