Modifiedculinary health fundPolicy N/A

Spinal Muscular Atrophy - Gene Therapy - Zolgensma Utilization Management Medical Policy

Defines prior authorization, clinical and laboratory criteria, dosing, kit/NDC mapping, and exclusions for medical benefit coverage of intravenous Zolgensma for treatment of spinal muscular atrophy in patients under 2 years of age.

Policy Summary

Payerculinary health fund

PolicySpinal Muscular Atrophy - Gene Therapy - Zolgensma Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeMODIFIED

Effective Date

Next Review Date

Key ActionPrior authorization is recommended; obtain required documentation (genetic test confirming bi-allelic SMN1 variants, anti-AAV9 titer, recent liver/renal/CBC labs, current weight, and prior Zolgensma/Itvisma records) and note approvals are one-time with a 90-day authorization window.

POLICY UPDATE CHANGES

Itvisma was added as a gene therapy that the patient should not have received previously.

Hemoglobin criterion changed to 'within the normal reference range' from a fixed numeric range.

Approval duration changed from 30 days to 90 days.

Added clarification that all approvals are one-time (per lifetime) single dose and verification of weight-based dosing is required by Medical Director.

Removed prior requirement that systemic corticosteroids equivalent to prednisolone 1 mg/kg/day be started 1 day prior and continued for 30 days.

Added definition that full-term gestational age may be defined as postmenstrual age ≥ 39 weeks and 0 days.

Coverage Summary

Covered with criteria: Intravenous Zolgensma (onasemnogene abeparvovec) is approved as a one-time (per lifetime) single dose for patients with genetically confirmed spinal muscular atrophy (biallelic SMN1 pathogenic variants) who are 2 years of age or younger, when all clinical and laboratory criteria are met. Prior authorization is required and approvals are provided as a single dose at 1.1 x 10^14 vg/kg IV based on current weight, with an authorization window of 90 days to prepare and administer therapy. Verification is required to confirm the patient has not previously received Zolgensma or Itvisma; if claims history is unavailable, the prescribing physician must confirm absence of prior gene therapy.

Key laboratory and clinical thresholds that must be met include baseline anti-AAV9 antibody titers ≤ 1:50, liver tests (ALT, AST, total bilirubin, prothrombin time) each ≤ 2 x ULN, creatinine < 1.0 mg/dL, white blood cell count ≤ 20,000 cells/mm3, and hemoglobin within the normal reference range for age/gender. SMN2 copy number requirements and weight documentation windows are specified in the criteria and must be documented.

Key thresholds

AgePatient is < 2 years of age

Anti-AAV9 titerBaseline anti-AAV9 antibody titers ≤ 1:50

Dose1.1 x 10^14 vector genomes per kg (vg/kg) IV, single dose (one-time per lifetime)

Approval duration90 days to allow preparation and administration

Lab windowsLiver, renal, and CBC testing within the past 30 days; specific liver criteria: ALT ≤ 2 x ULN, AST ≤ 2 x ULN, total bilirubin ≤ 2 x ULN (neonatal jaundice acceptable), PT ≤ 2 x ULN; creatinine < 1.0 mg/dL; WBC ≤ 20,000 cells/mm3; hemoglobin within lab/age/gender reference range

Weight documentation windowCurrent patient body weight obtained within the past 14 days

Full-term gestational age definitionFull-term (postmenstrual age) defined as ≥ 39 weeks and 0 days (gestational age plus chronological age)

Initial (one-time) Approval Criteria

FDA-Approved Indication - Initial (one-time) approval criteria

Approve for a one-time (per lifetime) single dose if the patient meets ALL of the following (A through N):

ALL of the following

A: Patient is < 2 years of age
B: If the patient is a premature neonate, full-term gestational age of 39 weeks and 0 days has been met
Full-term gestational age can be defined as the postmenstrual age (gestational age plus chronological age) being equal to ≥ 39 weeks and 0 days.
C: Patient has not received Zolgensma or Itvisma (onasemnogene abeparvovec-brve intrathecal injection) in the past
Verification in claims history required; if no claim for Zolgensma or Itvisma is present (or if claims history is not available), the prescribing physician confirms that the patient has not previously received Zolgensma or Itvisma.

Conditions Not Recommended for Approval

Do not recommend coverage in the following situations:

ANY of the following

1: Patient has complete paralysis of all limbs
Limitation of use per prescribing information; data lacking for advanced SMA.
2: Patient has permanent ventilator dependence
Limitation of use per prescribing information; data lacking for advanced SMA.
3: Administration to individuals in utero
Zolgensma not approved for in utero administration.

Applicable Codes

Zolgensma kit NDCs (per weight ranges / kit sizes listed)NDCCovered

71894-120-02	Kit for weight range 2.6 to 3.0 kg (Total vials per kit = 2)
71894-121-03	Kit for weight range 3.1 to 3.5 kg (Total vials per kit = 3)
71894-122-03	Kit for weight range 3.6 to 4.0 kg (Total vials per kit = 3)
71894-123-03	Kit for weight range 4.1 to 4.5 kg (Total vials per kit = 3)
71894-124-04	Kit for weight range 4.6 to 5.0 kg (Total vials per kit = 4)
71894-125-04	Kit for weight range 5.1 to 5.5 kg (Total vials per kit = 4)
71894-126-04	Kit for weight range 5.6 to 6.0 kg (Total vials per kit = 4)
71894-127-05	Kit for weight range 6.1 to 6.5 kg (Total vials per kit = 5)
71894-128-05	Kit for weight range 6.6 to 7.0 kg (Total vials per kit = 5)
71894-129-05	Kit for weight range 7.1 to 7.5 kg (Total vials per kit = 5)

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Provider Actions & Authorization Requirements

Prior Authorization

Prior authorization required

Prior authorization is recommended for medical benefit coverage; approvals provided for a one-time (per lifetime) single dose and authorization duration is 90 days to prepare and administer therapy. Note: dose preparation/administration timeframe allowed by the authorization duration.

Approval is one-time (per lifetime) single dose
Authorization duration: 90 days
Dose preparation note: 90-day window to prepare and administer therapy

Documentation Required

Documentation requirements

Documentation required includes genetic test results confirming bi-allelic SMN1 pathogenic variants, baseline anti-AAV9 titer, recent liver, renal, and CBC laboratory results, current body weight obtained within the past 14 days, and records/claims for prior Zolgensma or Itvisma; all documentation must include patient-specific identifiers.

Clinical Evidence

Key trials supporting efficacy include START and STR1VE (open-label, single-arm trials in symptomatic infants), SPR1NT (presymptomatic infants), and STR1VE-EU; these studies demonstrated improved survival and achievement of motor milestones in infants <2 years with bi-allelic SMN1 mutations.

Prescribing information and regulatory details are summarized in the Novartis Zolgensma IV prescribing information (February 2025), which is the cited source for trial data, dosing (1.1 x 10^14 vg/kg IV), and safety warnings.

Background

Zolgensma is an adeno-associated virus (AAV) vector-based, single-dose gene replacement therapy indicated for spinal muscular atrophy due to bi-allelic SMN1 mutations in patients younger than <2 years. The recommended administration is a one-time intravenous infusion dosed by weight at 1.1 x 10^14 vg/kg.

Safety concerns include a Boxed Warning for acute serious liver injury and acute liver failure; elevated aminotransferases have been observed and patients with preexisting liver impairment may be at higher risk. Clinical trials required baseline anti-AAV9 antibody testing and set an enrollment threshold of anti-AAV9 titers ≤ 1:50.

Because of these risks, baseline laboratory evaluations are required prior to infusion: liver function testing (ALT, AST, total bilirubin, prothrombin time), renal assessment including creatinine, and complete blood counts. Documentation of current body weight (within 14 days) is required to calculate the weight-based dose and dosing kits are customized by weight.

SMN2 copy number influences disease phenotype and treatment recommendations: fewer SMN2 copies generally predict more severe disease and inform urgency of treatment; criteria specify eligibility based on three or fewer SMN2 copies or specific quantitative confirmation when four copies are present.

In premature neonates, Zolgensma should be delayed until full-term gestational age is reached because concomitant corticosteroid exposure may adversely affect neurological development; full-term gestational age may be defined as postmenstrual age ≥ 39 weeks 0 days.

Definitions

Full-term gestational age (postmenstrual age): defined operationally as gestational age plus chronological age equal to ≥ 39 weeks and 0 days. For premature neonates, therapy should be delayed until this full-term postmenstrual age is reached.

One-time (per lifetime) single dose: Zolgensma is administered as a single intravenous infusion one time in a patient’s lifetime at a weight-based dose of 1.1 x 10^14 vg/kg; all approvals are provided for this single-dose, per-lifetime administration and dosing verification is required.

Operational note on premature neonates: because concomitant corticosteroid treatment may adversely affect neurological development, Zolgensma is not recommended for premature neonates until the operational full-term gestational age (postmenstrual age ≥ 39 weeks 0 days) has been met.

Revision History

2026-02-04revisedLatest

Approval duration changed from 30 days to 90 days to allow additional timeframe to prepare and administer the one-time dose.

2026-01-28revised

Hemoglobin requirement revised from a fixed numeric range (8–18 g/dL) to 'within the normal reference range' with note that reference ranges vary by laboratory, age, and gender.

2025-10-01revised

Clarified that all approvals are one-time (per lifetime) single dose and added verification of weight-based dosing by Medical Director; wording standardized regarding verification in claims history when available.