FDA Limitations on Eligible Patients for Bluebird's Skysona Due to Safety Woes
In a recent update, the Food and Drug Administration (FDA) has tightened the restrictions and labeling for bluebird bio's gene therapy Skysona (elivaldogene autotemcel), used to treat cerebral adrenoleukodystrophy (CALD). This decision comes in response to an increased risk of hematologic malignancy, including myelodysplastic syndrome and acute myeloid leukemia, following treatment.
The changes to the labeling include updates to the Boxed Warning, Indications and Usage, Warnings and Precautions, and Adverse Reactions sections, explicitly highlighting this higher risk of blood cancers post-treatment.
Skysona can now only be used in patients with CALD who have no available treatment alternatives or stem cell donors. The risk of hematologic malignancy is significant, with clinical trial data now showing about 15% of treated patients (10 out of 67) developing myelodysplastic syndrome or related malignancies, with occurrences ranging from 14 months to 10 years after treatment.
Patients receiving Skysona require life-long monitoring for hematologic malignancies. This includes complete blood counts at least every 3 months, assessments for clonal expansion at least twice in the first year and annually thereafter, and bone marrow evaluations as clinically indicated. If malignancy is detected, it must be reported promptly to the FDA and the manufacturer with guidance offered for further testing and management.
The FDA's decision reflects its cautious stance given the life-threatening nature of the malignancies and the severity of CALD. The agency is reserving Skysona for cases without better stem cell transplant options and ensuring rigorous long-term safety surveillance.
It is important to note that Skysona delivers functional copies of the ABCD1 gene into patients' stem cells, aiming to correct the genetic mutation causing CALD. However, the benefits of the therapy must be weighed against the risks, particularly the increased risk of hematologic malignancies.
This development in the gene therapy space comes amidst broader challenges and setbacks, including patient deaths associated with Sarepta's Duchenne muscular dystrophy therapy Elevidys and a Complete Response Letter from the FDA for Ultragenyx's Sanfilippo gene therapy due to manufacturing issues.
References: [1] FDA News Release. (2025, August). FDA strengthens warnings for Skysona (elivaldogene autotemcel) for cerebral adrenoleukodystrophy due to increased risk of hematologic malignancies. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-strengthens-warnings-skysona-elivaldogene-autotemcel-cerebral-adrenoleukodystrophy-due-increased-risk [2] bluebird bio. (2025, August). Important safety update: Skysona (elivaldogene autotemcel) for cerebral adrenoleukodystrophy. Retrieved from https://www.bluebirdbio.com/news/important-safety-update-skysona-elivaldogene-autotemcel-for-cerebral-adrenoleukodystrophy/ [3] National Organization for Rare Disorders. (n.d.). Cerebral adrenoleukodystrophy. Retrieved from https://rarediseases.org/rare-diseases/cerebral-adrenoleukodystrophy/ [4] Skysona Prescribing Information. (2022). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212989s000lbl.pdf [5] U.S. Food and Drug Administration. (2024, November). FDA warns of potential risks associated with Skysona (elivaldogene autotemcel) for cerebral adrenoleukodystrophy. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-warns-potential-risks-associated-skysona-elivaldogene-autotemcel-cerebral-adrenoleukodystrophy
