ModifiedCentenePolicy N/A

Elivaldogene Autotemcel (Skysona) — Coverage Criteria

Medical necessity and prior authorization criteria for Skysona (elivaldogene autotemcel) for early, active cerebral adrenoleukodystrophy (CALD) in pediatric patients across Centene-affiliated plans (Commercial, HIM, Medicaid).

Policy Summary

PayerCentene

PolicyElivaldogene Autotemcel (Skysona) — Coverage Criteria

Policy CodePolicy N/A

Change TypeMaterial updates to coverage and attestation requirements

Effective DateSep 16, 2022

Next Review DateN/A

Key ActionSubmit prior authorization with transplant and hematology specialist attestations and documentation showing member meets all approval criteria, including minimum dose of 5.0 x 10^6 CD34+ cells/kg.

SourceLink

POLICY UPDATE CHANGES

Added criterion that the member does not have an available HLA-matched donor and understands risks/benefits of alternative options such as allogeneic HSCT.

Added requirement for attestation from transplant specialist that member is clinically stable.

Added requirement for hematology specialist attestation and hematologic assessments for CALD with isolated pyramidal tract disease.

Added exclusion for HIV-1 and HIV-2.

Updated dosing criterion to a minimum dose per FDA labeling and clarified Skysona is dosed one time only.

Removed Appendix E VLCFA lab reference ranges and added hematologic malignancy information to Appendix D.

4-17approved patient age range

Loes 0.5-9permitted Loes score range

NFS <1neurologic function requirement

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Min 5 x10^6required dose cell content

One-timeapproval duration

Boxed warningsafety risk

Coverage Criteria

inv-01: Initial Therapy — Covered when ALL of the following are met for initial (one-time) therapy.

Covered when ALL of the following are met for initial (one-time) therapy:

Diagnosis of adrenoleukodystrophy with genetic confirmation of ABCD1 mutation and elevated very long chain fatty acids (VLCFA).

chunks 6

Prescribing clinicians: Prescribed by or in consultation with both a neurologist and a transplant specialist.

chunk 6

Patient age and sex: Patient is a biologic male aged 4 through 17 years.Age 4-17; biologic male

chunk 6

Disease activity and severity: Early, active cerebral ALD defined by brain MRI demonstrating gadolinium-enhancing demyelinating lesions with Loes score >= 0.5 and < 9 on the 34-point scale, and neurologic function score (NFS) < 1.Loes 0.5-9; NFS <1

chunks 6,19

Transplant candidacy/alternatives: Either: (a) no available full HLA-matched donor with submitted medical rationale that allogeneic HSCT is not feasible, OR (b) an available HLA-matched donor plus documentation that the member understands the risks and benefits of alternative therapeutic options such as allogeneic HSCT; in all cases transplant specialist attests member is clinically stable and eligible for myeloablative conditioning and HSCT.

chunk 6

Prior therapies and gene therapy history: Member has not received prior allogeneic hematopoietic stem cell transplantation (HSCT) and has not previously received gene therapy; member (or caregiver) understands the potential increased risk of malignancy associated with Skysona.

chunk 6

Safety and baseline testing: Member is negative for HIV-1 and HIV-2; for members with CALD and isolated pyramidal tract disease, hematology specialist attestation that applicable baseline hematologic assessments have been performed per Appendix E.HIV negative

chunks 6,18

Product dose requirement: Product dose must contain a minimum of 5.0 x 10^6 CD34+ cells/kg.>= 5.0 x 10^6 CD34+ cells/kg

chunk 19

inv-02: Continuation Therapy — Continuation therapy rules (note: treatment is one-time only per policy).

Continuation therapy

Continuation: Continued therapy is not authorized; Skysona is indicated to be administered one time only (one-time infusion per lifetime).

chunks 10,7

inv-03: Coverage criteria (summary) — Policy-level summary of changes and requirements (all must be met).

Covered when ALL of the following are met (policy-level summary of changes and requirements):

Overall coverage preconditions: Member meets FDA-labeled indications for Skysona and authorization is for a single administration only at a minimum dose of 5.0 x 10^6 CD34+ cells/kg; prior authorization is required and all requests require medical director review.Minimum dose 5.0 x 10^6; single administration

chunks 23,19,4

Donor/HSCT considerations and attestations: Member does not have an available full HLA-matched donor or, if a donor exists, documentation that the member understands risks/benefits of alternatives such as allogeneic HSCT; require attestation from a transplant specialist that the member is clinically stable and eligible for myeloablative conditioning and HSCT.

chunk 23

Hematologic assessments and attestation: For CALD with isolated pyramidal tract disease require hematology specialist attestation that the member understands malignancy risk and has completed baseline hematologic assessments listed in Appendix E (CBC with differential; hematopathology review of bone marrow with flow cytometry, karyotyping, and NGS panel; peripheral blood smear review; testing for germline mutations associated with hematologic malignancy).

Requests for indications that are not FDA‑approved for elivaldogene autotemcel (Skysona) will not be authorized unless the request is supported by applicable off‑label use policy documentation or other evidence of coverage. Providers should include citation to the referenced off‑label use policy (e.g., CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage when requesting prior authorization for a non‑labeled indication.

Active infection with HIV‑1 or HIV‑2 is an exclusion for coverage of Skysona. Presence of either infection should be documented and will preclude authorization per the policy exclusion.

Skysona is intended to be administered as a one-time therapy only. Continued therapy or repeat dosing is not authorized; approval duration is documented as not applicable for ongoing/continuous treatment because the product is given a single time per patient.

Coding and Dosing

Referenced billing codesHCPCS

J3590	Unclassified biologics
C9399	Unclassified drugs or biologicals

Referenced billing codes (duplicate source entry)HCPCS

J3590	Unclassified biologics
C9399	Unclassified drugs or biologicals

Minimum CD34+ cells/kg

Minimum CD34+ cells/kg>= 5.0 x 10^6 CD34+ cells/kg

Source contextDose contains a minimum of 5 x 10^6 CD34+ cells/kg (Dosage and Administration).

Related dosing noteMinimum recommended dose for CALD per dosing guidance: 5.0 x 10^6.

Loes score

Loes score range>= 0.5 and < 9 on the 34-point scale

DefinitionThe Loes score rates severity of MRI brain abnormalities from 0 to 34; higher scores indicate greater severity.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required / Supportive Documentation

Prior authorization required. Requests must indicate FDA-consistent dosing and single administration; approval duration is for a one-time infusion. Provider must submit supporting documentation (office notes, labs, other clinical information) demonstrating that the member meets all applicable criteria. All requests are subject to medical director review.

Approval duration: 3 months (one-time infusion per lifetime)
Dose must meet minimum of 5.0 x 10^6 CD34+ cells/kg per FDA labeling
Provider must supply office notes, laboratory results, and other clinical documentation to support the request
All requests require medical director review

Billing Rule

Background

Skysona (elivaldogene autotemcel) is a genetically modified, autologous CD34+ hematopoietic stem cell product in which patient‑derived CD34+ cells are transduced ex vivo with a lentiviral vector encoding ABCD1 cDNA. The product is intended to deliver a functional ABCD1 gene to hematopoietic stem cells to slow neurologic progression in early, active cerebral adrenoleukodystrophy (CALD). Per policy and dosing guidance, Skysona is given as a single, one‑time infusion with a minimum recommended dose of 5.0 x 10^6 CD34+ cells/kg for eligible patients.

Definitions and Terms

Elivaldogene autotemcel (Skysona)

Product descriptionElivaldogene autotemcel (Skysona) is a genetically modified autologous CD34+ cell–enriched population of hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding ABCD1 cDNA.

Therapeutic intentDesigned to slow progression of neurologic dysfunction in early, active cerebral adrenoleukodystrophy (CALD) in eligible pediatric patients.

AdministrationAutologous cell product prepared ex vivo and administered as a single infusion per labeling and policy criteria.

Major functional disability (MFD)-free survival

DefinitionMajor functional disability (MFD)-free survival was the endpoint used for accelerated approval; 24-month MFD-free survival was referenced in initial approval.

Relevance

Revision History

2024-07-19annual_review

4Q 2024 annual review: removed Appendix E VLCFA lab reference ranges and added hematologic malignancy information to Appendix D; references reviewed and updated.

2023-07-10annual_review

4Q 2023 annual review: references reviewed and updated (no significant changes noted in clinical policy text).

2023-11-24pandt_approval

P&T approval recorded for 4Q 2023 annual review.

Policy Summary

PayerCentene

PolicyElivaldogene Autotemcel (Skysona) — Coverage Criteria

Policy CodePolicy N/A

Change TypeMaterial updates to coverage and attestation requirements

Effective DateSep 16, 2022

Next Review DateN/A

SourceLink

On This Page

Exclusions and safety: No active HIV-1 or HIV-2 infection; provider must document understanding of Boxed warning risk for hematologic malignancy and submit supporting documentation (office chart notes, labs) with the request.HIV negative

chunks 23,4,18

Context for eligibility

Required to qualify as early, active CALD per initial approval criteria.

Neurologic Function Score (NFS)

Neurologic Function Score (NFS) requirementNFS < 1

DefinitionNFS is a 25-point score assessing gross neurologic dysfunction; 0 indicates no observed impairment and higher scores indicate greater deficits.

Role in eligibilityNFS <1 identifies asymptomatic or mildly symptomatic patients eligible for Skysona per FDA indication.

Minimum dose

Minimum recommended dose5.0 x 10^6 CD34+ cells/kg (minimum recommended dose)

Dosing frequencySkysona is administered one time only (single infusion).

Maximum doseNone specified in dosing guidance.

Dosing and Coding for Prior Authorization

Prior authorization dosing must reflect FDA labeling: minimum dose 5.0 x 10^6 CD34+ cells/kg. Skysona is indicated as a single administration (one-time infusion per lifetime); prior authorization requests and approval should be for a single administration. Include coding/billing documentation consistent with a one-time gene therapy administration.

Minimum dose: 5.0 x 10^6 CD34+ cells/kg (per FDA)
Single administration only — one-time infusion per lifetime
Ensure coding and billing denote gene therapy one-time administration

Denial Risk

Non‑FDA Indications

Requests for indications that are not FDA-approved are not authorized under this policy unless supported by the plan’s off‑label use policies or specific evidence of coverage. Providers must reference and document alignment with applicable off-label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid) as applicable.

Non‑FDA indications require documentation of efficacy/safety per applicable off‑label use policy (CP.CPA.09, HIM.PA.154, CP.PMN.53)

Documentation Required

Alternative Therapy Consideration

Because of the risk of hematologic malignancy associated with treatment, providers must document consideration of alternative therapies, including allogeneic hematopoietic stem cell transplantation (HSCT). If an HLA‑matched donor exists, HSCT should be considered; if HSCT is not feasible, provider must submit medical rationale (for example donor inability to undergo donation or other medical contraindications).

Document consideration of alternative therapies including allogeneic HSCT
If HSCT not feasible, submit medical rationale (e.g., donor unable to undergo donation procedure, medical contraindications)
Provider must document that risks/benefits of alternative options were discussed with member/family

Documentation Required

Alternative Donor / HSCT Consideration and Transplant Specialist Attestation

Member must not have an available full HLA‑matched donor unless the member and provider document that HSCT is not feasible or that the member understands and declines HSCT after discussion of risks/benefits. Transplant specialist attestation is required that the member is clinically stable, eligible for myeloablative conditioning and HSCT, and that alternatives (including presence or absence of an HLA‑matched donor) were discussed.

Attestation from a transplant specialist that member is clinically stable and eligible for myeloablative conditioning and HSCT
Documentation that member does not have an available full HLA‑matched donor OR documented rationale why HSCT is not feasible
Member understands risks and benefits of alternative therapeutic options such as allogeneic HSCT

Denial Risk

Exclusion — HIV

Presence of HIV‑1 or HIV‑2 is an exclusion under this policy and may result in denial of authorization. Verify HIV status and document negative testing per plan requirements prior to approval.

Member must be negative for HIV‑1 and HIV‑2; positive status is an explicit exclusion

Accelerated approval for Skysona was based on 24-month MFD-free survival; continued approval may depend on confirmatory trial verification of clinical benefit.

Clinical implicationMFD-free survival measures absence of major functional disability and is used to assess long-term clinical benefit of treatment.

NFS — Neurologic Function Score

NFS definitionNeurologic Function Score (NFS) is a 25-point score used to evaluate severity of gross neurologic dysfunction across multiple symptoms; 0 indicates no observed impairment.

Use in policyNFS <1 is required to identify asymptomatic or mildly symptomatic patients eligible for Skysona.

Scoring implicationHigher NFS corresponds to increasing severity of functional deficits.

MFD — Major Functional Disability

MFD definitionMFD stands for Major Functional Disability, an outcome indicating significant loss of neurologic function; absence of MFD underlies MFD-free survival endpoint.

Regulatory roleMFD occurrence (or freedom from MFD) was a key endpoint supporting accelerated approval of Skysona.

Clinical relevancePrevention or delay of MFD is a primary therapeutic goal in treating early, active CALD.

VLCFA — Very long chain fatty acids

VLCFA definitionVLCFA stands for very long chain fatty acids (elevated levels are part of diagnostic criteria for adrenoleukodystrophy).

Diagnostic roleElevated VLCFA levels, together with genetic confirmation of ABCD1 mutation, support diagnosis of adrenoleukodystrophy.

Mention in dosing/administrationVLCFA is listed among terms in the Dosage and Administration section and initial approval criteria.

2022-09-16policy_effectiveLatest

Policy effective date recorded (policy modified to add requirements including transplant specialist attestation, hematology attestations, HIV exclusion, and updated minimum dosing per FDA labeling).