ModifiedColorado Rocky Mountain Health PlansPolicy IEXD0079.10

Zolgensma (Onasemnogene abeparvovec-xioi) coverage

Defines medical necessity and coverage criteria for a one-time intravenous infusion of Zolgensma for treatment of spinal muscular atrophy (SMA) in eligible pediatric patients under Individual Exchange benefit plans (excludes MA, NV, NY).

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyZolgensma (Onasemnogene abeparvovec-xioi) coverage

Policy CodePolicy IEXD0079.10

Change TypeRevised coverage criterion added

Effective DateDec 1, 2025

Next Review Date

Key ActionPrior authorization required; do not request a planned inpatient admission 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 patient age for coverage

1:50max anti-AAV9 titer

J3399HCPCS code listed

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Coverage Criteria for Zolgensma (Onasemnogene abeparvovec-xioi)

Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met:

Genetic confirmation: Submission of medical records confirming mutation or deletion of genes in chromosome 5q resulting in homozygous SMN1 deletion/mutation or compound heterozygous SMN1 mutation (e.g., homozygous deletion of exon 7 at locus 5q13).

e.g., homozygous deletion of exon 7 at locus 5q13

Diagnosis requirement: Either: diagnosis of symptomatic SMA by a neurologist with expertise in SMA; OR diagnosis based on newborn screening plus documentation that the patient has four or fewer SMN2 gene copies (with submission of supporting medical records).≤ 4 SMN2 copies for newborn-screen–identified patients

Age and gestational requirements: For neonates born prematurely, full-term gestational age must have been reached; patient must be less than 2 years of age at time of treatment.< 2 years

Respiratory support exclusion: Patient is not dependent on invasive ventilation or tracheostomy, and not dependent on non‑invasive ventilation except for naps and nighttime sleep.

Prescriber and administration: Zolgensma is prescribed by a neurologist with expertise in the treatment of SMA and will be administered intravenously in accordance with FDA‑approved labeling.

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

Immunologic and prophylaxis requirements: Patient does not have an elevated anti‑AAV9 antibody titer above 1:50 and will receive prophylactic prednisolone (or equivalent glucocorticoid) prior to and following receipt of Zolgensma per FDA labeling.anti‑AAV9 ≤ 1:50

Lifetime and timing limits: Patient has never received Zolgensma previously; authorization is limited to one treatment per lifetime and will be issued for no longer than 45 days from approval or until the patient reaches 2 years of age, whichever is first.one lifetime dose

Coverage rationale and constraints

Coverage and use are guided by FDA indication, expert consensus, and updated payer criteria (see revisions).

FDA Indication: Onasemnogene abeparvovec (Zolgensma) is indicated for pediatric patients less than 2 years of age with spinal muscular atrophy and bi‑allelic SMN1 mutations.age < 2 years, bi‑allelic SMN1 mutation

Informational — FDA labeling

Limitations of Use: Repeat administration has not been evaluated; safety and effectiveness in patients with advanced SMA (e.g., complete limb paralysis, permanent ventilator dependence) have not been evaluated.

FDA limitations of use

Expert consensus considerations: SMN2 copy number should be determined urgently and guide treatment decisions in presymptomatic infants; early initiation of disease‑modifying therapy is associated with better outcomes. Older or heavier patients have limited data and increased risk; alternative approaches (including discussion of other disease‑modifying treatments or intrathecal administration where investigational) should be considered per European consensus.

For pre-symptomatic infants identified by newborn screening, treatment decisions should incorporate SMN2 copy number. This policy follows the guidance that pre-symptomatic patients with more than four SMN2 copies are not appropriate candidates for Zolgensma under the plan's coverage determination. For later-onset symptomatic SMA, intravenous onasemnogene abeparvovec is limited to pediatric patients younger than 2 years of age; patients with symptomatic onset beyond 2 years are excluded from coverage. Additionally, SMA that does not involve chromosome 5q mutations or deletions is not eligible for coverage under this policy.

Use of onasemnogene abeparvovec in patients with advanced SMA (for example, complete paralysis of the limbs or permanent ventilator dependence) has not been evaluated and therefore is not supported by current evidence for routine coverage. The 2024 European consensus further cautions that intravenous gene replacement for older or heavier patients should only be done under a rigorous protocol with continuous safety and efficacy monitoring, and notes that treatment of patients above 21 kg cannot be recommended.

This therapy is considered not proven/ not medically necessary for the following populations: pre-symptomatic infants with >4 SMN2 copies, symptomatic patients with disease onset after 2 years of age, and patients with SMA that does not involve 5q SMN1 mutations or deletions. Routine combination (concomitant) use of Zolgensma with other SMN-modifying therapies is also not considered medically necessary.

Repeat administration of onasemnogene abeparvovec has not been evaluated in clinical studies; therefore subsequent doses or re-administration are not supported by the available evidence and are not covered under this policy.

Coding and Clinical Thresholds

Applicable HCPCS/CPT 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 threshold — eligibility cutoff value

Eligibility cutoffAnti-AAV9 antibody titer must be <= 1:50; patients with antibody titer above 1:50 are excluded

Test typeSerologic measurement of anti-AAV9 neutralizing antibodies (per policy requirement)

Action on high titerRequests will be denied if anti-AAV9 antibody titer is above 1:50

inv-10: SMN2 copy number — urgency and distinction guidance

Urgency triggerSMN2 copy number ≤ 3 indicates urgent need for disease-modifying treatment

Presymptomatic guidanceFor infants identified by newborn screening, determine SMN2 copy number urgently to guide timing of therapy

Provider Actions, Authorization, and Documentation

Step Therapy

Therapy sequencing considerations

Consideration of alternative therapies and sequencing is required prior to Zolgensma administration. Because risk increases with dose (which is proportional to patient weight and age), heavier and older patients should be treated very cautiously; alternative disease‑modifying treatments or future intrathecal administration of onasemnogene abeparvovec should be considered and discussed with families. In the absence of convincing evidence that combining gene therapy with other SMN‑modifying treatments offers superior outcomes, routine combination therapy is not recommended outside of a controlled clinical trial.

Consider alternatives including nusinersen (Spinraza) or risdiplam (Evrysdi); discuss risks/benefits with parents/caregivers
For older/heavier patients, consider cautious approach and evaluate eligibility for alternative treatments or enrollment in rigorous protocols with continuous safety/efficacy monitoring
Avoid routine combinatorial therapy of gene replacement plus another SMN‑modifying agent outside clinical trials
For newborns identified by newborn screening, determine SMN2 copy number urgently and initiate treatment without delay when indicated

Background and Clinical Context

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused primarily by biallelic pathogenic variants of SMN1, resulting in loss of SMN protein and motor neuron degeneration. The paralogous gene SMN2 does not fully compensate for SMN1 loss, and the patient’s SMN2 copy number correlates with disease severity and guides urgency of treatment decisions; lower copy number (≤ 3) indicates greater urgency for disease‑modifying therapy. Zolgensma is an adeno-associated virus 9 (AAV9) mediated one-time SMN1 gene replacement therapy administered intravenously to eligible pediatric patients and is intended to provide sustained SMN protein expression.

Key Definitions

inv-21: SMN1 / SMN2 — definitions of the genes and clinical relevance

SMN1 definitionPrimary gene whose biallelic (homozygous) loss causes spinal muscular atrophy (e.g., homozygous deletion of exon 7 at locus 5q13)

SMN2 definitionParalogous gene; the number of SMN2 copies correlates with SMA phenotype severity and progression

Clinical relevanceConfirmatory testing should include number of SMN1 and SMN2 copies to inform diagnosis and treatment urgency

inv-22: Anti-AAV9 antibody titer — definition and policy threshold

DefinitionSerologic measure of antibodies against AAV9 used to determine eligibility for intravenous onasemnogene abeparvovec

Policy thresholdPatient must not have an elevated anti-AAV9 antibody titer above 1:50 to be eligible