FDA

FDA restricts Skysona use due to hematologic malignancy risk

August 11, 2025

On August 7, 2025, FDA mandated significant labeling changes for Skysona (elivaldogene autotemcel), a lentiviral autologous hematopoietic stem cell gene therapy approved in 2022 under accelerated approval for boys aged 4 to 17 with early, active cerebral adrenoleukodystrophy (CALD). The therapy was originally approved based on 24-month Major Functional Disability-free survival, with a boxed warning for hematologic malignancy risk.

At the time of initial approval of Skysona in 2022, hematologic malignancy was identified as a serious risk, with myelodysplastic syndrome (MDS) reported in 3 of 67 patients (4%) across clinical studies. Since that initial approval, FDA has received seven additional reports from clinical trial participants, and as of July 2025, hematologic malignancies have been diagnosed in 10/67 (15%) clinical trial participants, more than tripling the previously reported incidence. Nine of the 10 patients have been treated with allogeneic hematopoietic stem cell (allo-HSCT; with or without chemotherapy) for the hematologic malignancy.

Current reports suggest that the time to diagnosis of hematologic malignancy ranges from 14 months to 10 years after Skysona administration. The malignancies are life-threatening conditions, and one death related to treatment for malignancy has occurred. One patient developed recurrence of MDS after initial treatment, which required re-treatment. Notably, some patients developed malignancy before Skysona had time to potentially provide therapeutic benefit for their CALD.

Following a review of the clinical trial data, FDA is requiring updates to the Boxed Warning, Indications and Usage, Warnings and Precautions, and Adverse Reactions – Clinical Trials Experience sections of the prescribing information and Medication Guide to include new safety information on the increased risk of hematologic malignancy. Notably, the revised Indications and Usage restricts the indication to patients without an available human leukocyte antigen (HLA)-matched allo-HSC donor. Therefore, Skysona should only be used in CALD patients without suitable alternative treatment options, given the increased risk of hematologic malignancy. The Limitations of Use section retains language emphasizing careful consideration of appropriateness and timing of treatment.

To report suspected adverse events including hematologic malignancies, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Source:

FDA Approved Required Labeling Changes for Increased Risk of Hematologic Malignancy Following Treatmetn with Skysona (elivaldogene autotemcel) [News release]. 2025. https://www.fda.gov/vaccines-blood-biologics/fda-approves-required-labeling-changes-increased-risk-hematologic-malignancy-following-treatment