Mass General Brigham Health Plan Skysona Coverage Update

Medical Necessity Criteria for Skysona (Initial Approval)

Initial Approval — Medical Necessity Criteria

Authorization of a single treatment may be granted to members 4 to 17 years of age for treatment of early, active cerebral adrenoleukodystrophy (CALD) when ALL of the following criteria are met:

ALL of the following

Member age between 4 and 17 years
Elevated plasma very long chain fatty acid levels according to the performing laboratory's standard reference values
ALL of the following
- Clinical or laboratory evidence consistent with adrenoleukodystrophy (as documented)
- Presence of a variant in the ABCD1 gene as detected by genetic testing
ALL of the following
- Loes score between 0.5 and 9 (inclusive) on the 34-point scale
- Neurologic Function Score (NFS) less than or equal to 1
- Gadolinium enhancement on MRI of demyelinating lesions
Member is eligible for hematopoietic stem cell transplant (HSCT) but an HLA-matched family donor is not available; HLA matching with family members should be explored
Documentation of timing/plan required
Member has not taken antiretroviral medication(s) for at least one month prior to mobilization, OR the expected duration for elimination of the antiretroviral(s) until all cycles of apheresis are completed
Member has not received a vaccination during the 6 weeks preceding the start of myeloablative conditioning and until hematological recovery following treatment
Documentation of planned testing is required
ALL of the following
- Member tests negative for HIV-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), and Human T-lymphotropic virus 1 & 2 (HTLV-1/HTLV-2) in accordance with clinical guidelines before collection of cells for manufacturing
ANY of the following
- Alanine transaminase (ALT) value less than 2.5 x upper limit of normal (ULN)
- Aspartate transaminase (AST) value less than 2.5 x ULN
- Total bilirubin value less than 3.0 mg/dL (except if diagnosis of Gilbert's Syndrome); and the member is otherwise stable
Member does not have any current malignancies
Member has not previously received Skysona or any other gene therapy

Dosing, Administration, and Duration

Coverage conditions related to dosing and administration:

ALL of the following

Single-dose treatment course (one-time infusion)
Recommended dose: single IV dose containing a minimum of 5.0 x 10^6 CD34+ cells/kg of body weight based on weight prior to first apheresis>= 5.0 x 10^6 CD34+ cells/kg
Full myeloablative and lymphodepleting conditioning must be administered before infusion of Skysona
Member should receive seizure, hepatic veno-occlusive disease, anti-fungal, and antibiotic prophylaxis as needed

Facility and Provider Requirements

Treatment setting and prescribing provider requirements:

ALL of the following

Medication must be prescribed by a hematologist, neurologist, and/or a stem cell transplant specialist
Treatment must be administered at a Skysona Qualified Treatment Center

Not Covered / Exclusions

Explicit exclusions and non-covered scenarios:

ALL of the following

Members with an available appropriate HLA-matched family donor who are eligible for HSCT are not considered appropriate for Skysona per policy preference for HSCT when donor available
Members with current malignancies are excluded
Additional (repeat) courses of Skysona are considered experimental/investigational and not covered

Numeric and Clinical Thresholds

Eligibility and Laboratory Thresholds

Age4 to 17 years

Loes score0.5 to 9 (inclusive) on the 34-point scale

Neurologic Function Score (NFS)≤ 1

Minimum CD34+ cell dose≥ 5.0 x 10^6 CD34+ cells/kg (based on weight prior to first apheresis)

ALT< 2.5 x ULN

AST< 2.5 x ULN

Total bilirubin< 3.0 mg/dL (except if diagnosis of Gilbert's Syndrome)

Authorization, Documentation, and Site Requirements

Prior Authorization

Prior authorization required (plan-dependent)

Authorization is required for Commercial and Qualified Health Plans, One Care, and Senior Care Options; for Mass General Brigham ACO members prior authorization is managed by the MassHealth Drug Utilization Review Program. Providers must submit documentation showing all medical necessity criteria are met.

J3590 (informational HCPCS code listed in policy)

Documentation Required

Required diagnostic and laboratory documentation

Provide documentation that supports diagnosis and eligibility including biochemical, genetic, imaging, neurologic, infectious disease, hepatic, vaccination, and HSCT donor search information as follows.

Elevated plasma very long chain fatty acid (VLCFA) levels per performing laboratory reference

Billing and Informational Codes

Informational codes included in policyHCPCS

J3590

Unclassified biologics (listed for informational purposes only; inclusion does not constitute coverage/reimbursement)

Clinical and Safety Context

Skysona (elivaldogene autotemcel, eli-cel) is an autologous hematopoietic stem cell lentiviral gene therapy that received FDA accelerated approval in September 2022 for the treatment of confirmed early, active cerebral adrenoleukodystrophy (CALD) in pediatric patients. The pivotal STARBEAM (ALD-102) trial and subsequent reports demonstrated high rates of sustained disease stabilization and major functional disability–free survival (for example, 94% MFD-free survival at a median follow-up of 29.4 months in the initial report and 81% at most recent follow-up in longer-term data), supporting the efficacy of a single-dose, autologous HSC gene therapy approach. (See clinical trial reports for study populations and outcomes.)

Post-trial and post-marketing data have raised significant safety concerns: cases of hematologic malignancy, including myelodysplastic syndrome and acute myeloid leukemia, were reported between approximately 14–92 months after treatment in patients enrolled in ALD-102 and ALD-104. These malignancies showed clonal vector insertion in oncogenes and clonal evolution, findings that have been attributed to factors such as the lentiviral vector design (strong MND promoter) and conditioning regimens (for example, fludarabine-containing regimens). Because of these risks, a REMS program and a boxed warning are in effect and long-term safety beyond five years remains uncertain.

Consensus guidance and recent expert reviews emphasize a preference for allogeneic hematopoietic stem cell transplantation (HSCT) for most patients with early-stage CALD when an appropriate HLA-matched donor is available. Skysona is considered a medically necessary alternative primarily for patients who do not have an available appropriate HLA-matched family donor and who otherwise meet the clinical and laboratory eligibility criteria consistent with the pivotal trials.

Operational and plan-specific notes: prior authorization requirements vary by product line (authorization is required for Commercial, One Care, and Senior Care Options; prior authorization for Mass General Brigham ACO members is managed through the MassHealth Drug Utilization Review Program), and updates to prior authorization tables and plan variations became effective in January 2026. The policy includes an informational HCPCS code J3590 for administrative purposes.

Defined Terms

Definitions

CALDCerebral adrenoleukodystrophy — early, inflammatory demyelinating form of X-linked adrenoleukodystrophy.

Loes scoreMRI-based 34-point severity scoring system for cerebral involvement in adrenoleukodystrophy; used to stage disease extent (policy requires Loes 0.5–9 for eligibility).

Neurologic Function Score (NFS)Clinical scale assessing neurologic function; policy requires NFS ≤ 1 for eligibility.

Skysona Qualified Treatment CenterFacility designated/qualified to administer Skysona per manufacturer and program requirements; treatment must be administered at a Skysona Qualified Treatment Center.

Policy Updates and Material Changes

2026-01Ad hoc update — Prior authorization table and One Care/SCO variationLatest

Updated prior authorization table and added variation for One Care and Senior Care Options (SCO) members (Effective January 2026).

April 2025Ad hoc update — MassHealth variation revised

MassHealth variation updated to include a new prior authorization process; prior authorization for Mass General Brigham ACO members is managed by the MassHealth Drug Utilization Review Program.

March 2025Ad hoc update — Content added

OpenPayer

Skysona (elivaldogene autotemcel) gene therapy for early, active cerebral adrenoleukodystrophy (CALD)

Medical Necessity Criteria for Skysona (Initial Approval)

Numeric and Clinical Thresholds

Authorization, Documentation, and Site Requirements

Billing and Informational Codes

Clinical and Safety Context

Defined Terms

Policy Updates and Material Changes