FDA restricts bluebird bio’s Skysona to CALD patients without suitable stem cell donors after higher blood cancer risk emerges

The FDA has updated Skysona’s label and restricted its use to CALD patients who lack an available HLA‑matched allogeneic stem cell donor453.

The restriction follows an FDA safety review linking Skysona to an increased risk of hematologic malignancies, including MDS and AML534.

As of July 2025, 10 of 67 treated patients (15%) in clinical trials developed blood cancers, up from 4% at the time of approval531.

The updated labeling includes changes to the Boxed Warning, Indications and Usage, Warnings and Precautions, and Adverse Reactions – Clinical Trials Experience54.

One treatment‑related death has occurred; most affected patients underwent allogeneic stem cell transplantation, with or without chemotherapy43.

Malignancies have been reported from approximately 14 months to up to 10 years after treatment, indicating a prolonged risk window31.

Skysona received accelerated approval in 2022 for early, active CALD, but was previously available to all eligible CALD patients with a boxed warning3.

FDA communication emphasized Skysona should only be used when no suitable alternative treatment options exist, given the malignancy risk5.

Sources:

1. https://www.packgene.com/frontier/080825-bluebird-bio/

3. https://www.biospace.com/policy/fda-restricts-patient-pool-for-bluebirds-skysona-amid-safety-concerns

4. https://www.aabb.org/news-resources/news/article/2025/08/12/fda-restricts-cald-gene-therapy-after-safety-review

5. https://www.cgtlive.com/view/fda-updates-labeling-bluebird-active-cerebral-adrenoleukodystrophy-gene-therapy-eli-cel-reflect-risk-hematologic-malignancy