ModifiedCentenePolicy CP.PHAR.556

Elivaldogene Autotemcel (Skysona) — coverage criteria for cerebral adrenoleukodystrophy

This policy defines medical necessity criteria, documentation and utilization review requirements for Skysona (elivaldogene autotemcel) for treatment of early, active cerebral adrenoleukodystrophy (CALD) in children and adolescents and applies to Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyElivaldogene Autotemcel (Skysona) — coverage criteria for cerebral adrenoleukodystrophy

Policy CodePolicy CP.PHAR.556

Change TypeMaterial revisions to criteria, PA routing, and HCPCS codes

Effective DateSep 16, 2022

Next Review Date

Key ActionSubmit prior authorization with documentation that all initial approval criteria are met for PDAC review.

SourceLink

POLICY UPDATE CHANGES

Updated FDA-approved indication to include lack of an available HLA-matched donor for allogeneic HSCT and removed criterion option for having an HLA-matched donor per prescribing information.

Updated prior authorization routing to redirect reviews to the Precision Drug Action Committee (PDAC) Utilization Management Review.

HCPCS code set updated: added J3387 and removed J3590 and C9399.

Criteria updated per FDA labeling: removed endocrinologist option; added transplant specialist requirement; clarified biologic male and age 4 to 17 years; added requirement that member does not have an available HLA-matched donor and understands alternative options such as allogeneic HSCT.

Added exclusion for HIV-1 and HIV-2 and hematologic malignancy information to appendices.

4-17 yrsage range for covered indication

NFS ≤ 1maximum neurologic function score allowed

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Loes 0.5–9allowed MRI Loes score range

≥5 x10^6 CD34+/kgminimum dose requirement

One-timedosing frequency

J3387HCPCS code added

Coverage Criteria for Skysona (elivaldogene autotemcel)

Initial Approval Criteria

Covered when ALL of the following are met

Diagnosis of adrenoleukodystrophy with both of the following: (a) genetic confirmation of ABCD1 mutation; and (b) elevated levels of very long chain fatty acids (VLCFA)

Prescriber: Prescribed by or in consultation with both a neurologist and a transplant specialist

Sex: Member is a biologic male

Age between 4 and 17 years

MRI disease activity: Brain MRI demonstrating both of the following: (a) Loes score ≥ 0.5 and ≤ 9 on the 34-point scale; and (b) gadolinium enhancement of demyelinating lesionsLoes 0.5–9

See Appendix D for Loes score details

Neurologic function: Member has a Neurologic Function Score (NFS) ≤ 1NFS ≤ 1

See Appendix D for NFS details

Donor availability: No available full HLA-matched donor (i.e., no available donor with full HLA-matching of all evaluated alleles)

Transplant eligibility: Transplant specialist attestation that member is clinically stable and eligible to undergo myeloablative conditioning and HSCT

Prior therapies: Member has not received prior allogeneic HSCT

Prior gene therapy: Member has not received prior gene therapy

Isolated pyramidal tract disease additional requirements: For members with CALD and isolated pyramidal tract disease: hematology specialist attestation that (a) member understands the potential increased risk of malignancy associated with Skysona treatment; and (b) applicable hematology assessments have been performed

See Appendix E for examples of hematology assessments

Infectious disease: Member is negative for HIV type 1 and HIV type 2

Dose requirement: Dose contains a minimum of 5 x 10^6 CD34+ cells/kg≥ 5 x 10^6 CD34+ cells/kg

Minimum recommended dose per FDA labeling

Initial therapy / coverage preconditions

Covered when ALL of the following are met per updated FDA-aligned criteria and policy changes:

Primary eligibility: Recipient is a biologic male aged 4 to 17 years; meets FDA labeling for Skysona; dosing is one time only; minimum dose per FDA labeling must be metage 4-17

Clarified in 4Q2022 and reflected in subsequent reviews

Specialist attestations: Attestation by a transplant specialist that member is clinically stable and eligible for myeloablative conditioning and HSCT; hematology specialist attestation required when applicable (e.g., isolated pyramidal tract disease). Endocrinologist option removed per FDA-aligned updates.

Specialist requirements added per FDA labeling

Donor availability and alternatives: Member does not have an available HLA-matched donor and has been informed of risks/benefits of alternative therapeutic options such as allogeneic HSCT

FDA-approved indication updated to include lack of an available HLA-matched donor (4Q2025)

Skysona is not indicated to treat endocrine manifestations of adrenoleukodystrophy; specifically, Skysona does not treat or prevent adrenal insufficiency. The product has not been studied for CALD secondary to head trauma, and immune responses to the therapy may limit persistence and efficacy in certain genetic subgroups. Requests for indications not addressed in this policy that are not FDA‑approved will be denied unless the provider supplies sufficient documentation meeting applicable off‑label use policies.

Coverage is excluded for members with documented HIV‑1 or HIV‑2 infection. Additionally, certain hematologic malignancy conditions and related risk information are addressed in the policy appendices and may preclude coverage; providers should review and document any applicable exclusions as described in the appendices.

Skysona is authorized as a one‑time administration only. Continued therapy will not be authorized and approval duration is not applicable for repeat or ongoing dosing.

Use of Skysona that does not meet the updated FDA‑aligned criteria in this policy will be considered not medically necessary and will be denied. Key requirements that must be documented with prior authorization include the member’s age (4–17 years), that the prescriber(s) include a neurologist and a transplant specialist with required attestations (and hematology attestation when applicable), and documentation that the member does not have an available full HLA‑matched donor and has been informed of alternative options such as allogeneic HSCT. All requests are routed through the PDAC utilization management review and must include the supporting clinical documentation specified in the policy.

Coding and Dose Parameters

HCPCS codes referenced/updatedHCPCS

J3387	Injection, elivaldogene autotemcel, per treatment
J3590	Unclassified biologics (removed)
C9399	Unclassified drugs or biologicals (removed)

Minimum CD34+ cell dose

Minimum CD34+ cell doseMinimum recommended dose: ≥ 5.0 × 10^6 CD34+ cells/kg

Maximum doseNo maximum dose specified

Approval duration relatedApproval is for a one-time infusion; approval duration: 3 months

Loes score

Loes score range (allowed)Loes score ≥ 0.5 and ≤ 9 on the 34-point scale

Loes score scaleLoes score ranges from 0 to 34, higher scores indicate greater severity

Clinical requirement

Provider Actions, Prior Authorization, and Documentation Requirements

Prior Authorization

Prior Authorization and PDAC Review

Prior Authorization Required. Prior authorization is required for requests for elivaldogene autotemcel (Skysona). All requests reviewed under this policy must be submitted to the Precision Drug Action Committee (PDAC) Utilization Management Review per CC.PHAR.21. Do not submit standard PA packages to other review queues; PDAC routing is mandatory.

PDAC Utilization Management Review required — refer to CC.PHAR.21 for submission process and supporting documentation guidance.
Prior authorization is required for initial and one-time gene therapy dosing only (no repeat dosing).

Prior Authorization

Prior Authorization Routing and Requirements

Routing: Prior authorization requests for elivaldogene autotemcel must be directed to PDAC Utilization Management Review. Include all clinical documentation at time of submission to support timely review. PDAC staff may request additional records or specialist attestations as part of the review.

Submit full clinical chart notes, genetic testing results, MRI reports (including Loes score and gadolinium enhancement), transplant specialist consultation/attestation, hematology assessments if applicable, and documentation of donor availability evaluation.

Definitions and Scoring Systems

Loes score definition

DefinitionLoes score is a rating of the severity of abnormalities in the brain found on MRI, based on location/extent of disease and atrophy

Scale range0 to 34 (0 = normal MRI; higher scores indicate increased severity of cerebral lesions)

Scoring basisPoint system derived from location and extent of disease and presence of atrophy, localized or diffuse

Neurologic Function Score (NFS)

DefinitionCALD Neurologic Function Score (NFS) is a 25-point score evaluating severity of gross neurologic dysfunction across 15 symptoms in six categories

InterpretationNFS of 0 indicates no observed impairment; higher scores correspond to increasing severity of functional deficits

Biomarker Requirements

VLCFA — biomarker requirement

Required biomarkerElevated very long chain fatty acids (VLCFA) are required as part of diagnostic confirmation of adrenoleukodystrophy for eligibility

Where documentedVLCFA elevation is specified in Initial Approval Criteria (diagnosis must include genetic confirmation of ABCD1 mutation and elevated VLCFA)

Role in policyServes as a diagnostic criterion (with ABCD1 mutation) to determine eligibility for Skysona per the coverage criteria

Background on Skysona and Indication

Skysona (elivaldogene autotemcel) is an autologous, ex vivo lentiviral vector‑transduced CD34+ hematopoietic stem/progenitor cell therapy. The product delivers an ABCD1 cDNA payload within the transduced CD34+ cell population with the intent of slowing neurologic progression of early, active cerebral adrenoleukodystrophy; it is supplied as a single‑dose cell suspension and is administered as a single treatment.

Policy Summary

PayerCentene

PolicyElivaldogene Autotemcel (Skysona) — coverage criteria for cerebral adrenoleukodystrophy

Policy CodePolicy CP.PHAR.556

Change TypeMaterial revisions to criteria, PA routing, and HCPCS codes

Effective DateSep 16, 2022

Next Review Date

Key ActionSubmit prior authorization with documentation that all initial approval criteria are met for PDAC review.

SourceLink

On This Page

Safety exclusions and assessments: Member understands the risk of hematologic malignancy and has completed applicable hematology assessments; excludes members positive for HIV-1 or HIV-2 and those with hematologic malignancy conditions referenced in appendices

Exclusions and assessment requirements added/clarified in reviews

Prior authorization and review: Prior authorization required; requests are redirected to the Precision Drug Action Committee (PDAC) Utilization Management Review and must include documentation supporting that member meets FDA-aligned clinical criteria and specialist attestations

PA routing to PDAC updated in policy reviews

Required as part of MRI demonstrating early, active CNS disease for eligibility

Neurologic Function Score (NFS)

Maximum allowed NFSNeurologic Function Score (NFS) ≤ 1 on the 25-point scale

NFS scale description25-point score assessing gross neurologic dysfunction; higher scores reflect worse function

Use in eligibilityRequired to establish neurologic function threshold for coverage of Skysona

If PDAC requires assistance with submission, follow the PDAC submission support procedures in CC.PHAR.21.

Step Therapy

Step Therapy / Repeat Dosing

Step therapy / Repeat Dosing. Elivaldogene autotemcel is intended as a one-time gene therapy dosing. No step therapy is required, and repeat dosing is not covered.

One-time infusion per lifetime; approval duration: 3 months for initial dose only.
No sequential or trial-of-therapy requirements apply prior to approval; repeat doses are not covered.

Documentation Required

Assessment of Alternatives (HSCT)

Assessment of Alternatives Required. Prior to approval, documentation must demonstrate evaluation of allogeneic HSCT as an alternative therapy and assessment of HLA-matched donor availability. If no suitable HLA-matched donor is available, include details of the donor search and transplant specialist attestation regarding eligibility for HSCT.

Transplant specialist attestation that member is clinically stable and eligible to undergo myeloablative conditioning and HSCT.
Documentation that no available HLA-matched donor exists (full HLA-matching of all evaluated alleles) or rationale why HSCT is not appropriate.

Documentation Required

Supporting Documentation and PDAC Review

Supporting Documentation and PDAC Review. Provider must submit documentation (office chart notes, lab results, imaging reports, genetic testing, specialist consults, and any other relevant clinical information) demonstrating that the member meets all approval criteria. PDAC will review submitted documentation and may request additional records or specialist attestations.

Required documentation includes but is not limited to: genetic confirmation of ABCD1 mutation; VLCFA levels; brain MRI with Loes score and gadolinium enhancement; transplant specialist consultation and attestation; hematology assessments when applicable (see Appendix E).
PDAC may require hematology specialist attestation for members with CALD and isolated pyramidal tract disease confirming member understanding of malignancy risk and completion of hematology assessments.

Documentation Required

Required Clinical Documentation

Required Clinical Documentation. Document that the member understands the potential increased risk of malignancy associated with treatment and that applicable hematology assessments have been completed when indicated. Include attestations from required specialists and the results of baseline hematologic testing where applicable.

Transplant specialist attestation of clinical stability and HSCT eligibility.
Hematology specialist attestation that member understands malignancy risk and that baseline hematologic assessments were performed (see Appendix E: CBC with differential; peripheral blood smear hematopathology review; bone marrow biopsy with flow cytometry, conventional karyotyping, and NGS; germline testing as appropriate).
Documentation of age, biologic sex, HIV-1/2 negative status, prior HSCT or gene therapy status, and dosing calculations (minimum 5 x 10^6 CD34+ cells/kg).

Denial Risk

Non‑covered Indications

Non‑covered Indications. Requests for uses not addressed in this policy (non‑FDA approved or off‑label indications) will be denied unless sufficient documentation of efficacy and safety is provided per applicable off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for HIX, CP.PMN.53 for Medicaid).

Off‑label requests must include supporting literature, rationale, and alignment with the referenced off‑label policies to be considered.
Absence of sufficient supporting evidence will result in denial for non‑covered indications.

Denial Risk

Denial Risks and Common Triggers

Denial Risks from Unmet Criteria. Requests lacking required FDA‑aligned criteria, missing specialist attestations, incomplete PDAC routing, or absent required documentation (genetic confirmation, VLCFA, MRI with Loes score and gadolinium enhancement, transplant and hematology attestations, HIV testing, donor availability evidence, dosing calculation) are at high risk for denial.

Common denial triggers: failure to route PA to PDAC; missing genetic confirmation of ABCD1 mutation; absent or incomplete MRI evidence (Loes score and gadolinium enhancement); lack of transplant specialist attestation regarding HSCT eligibility and donor availability; missing hematology assessments or attestations when required; prior allogeneic HSCT or prior gene therapy noted in history.
Ensure all required items are included in the initial submission to reduce delays and avoid denial.

PurposeUsed to assess neurologic function for eligibility and severity assessment in CALD

Skysona

Generic nameElivaldogene autotemcel

Brand nameSkysona

Product descriptionGenetically modified autologous CD34+ cell–enriched population transduced ex vivo with a lentiviral vector encoding ABCD1 cDNA

Product formulation

FormulationSingle-dose cell suspension (up to two infusion bags) of genetically modified autologous CD34+ enriched cells labeled for the recipient

Intended usePrepared as a one-time infusion product for treatment of CALD

Packaging noteMay be supplied in up to two infusion bags

VLCFA

DefinitionVLCFA = very long chain fatty acids, a biomarker relevant to the diagnosis of adrenoleukodystrophy

Role in diagnosisElevated VLCFA levels are required along with genetic confirmation of ABCD1 mutation for CALD diagnosis

Documented sourceVLCFA is listed in product availability and is an entry requirement in initial approval criteria