FDA Restricts Skysona Use After More Reports of Hematologic Malignancy

The Food and Drug Administration (FDA) has approved new safety labeling changes for Skysona (elivaldogene autotemcel) due to the increased risk of hematologic malignancy. 

Approved in 2022, Skysona is indicated to slow the progression of neurologic dysfunction in boys 4 to 17 years of age with early, active cerebral adrenoleukodystrophy (CALD). The one-time gene therapy is designed to add functional copies of the ABCD1 cDNA into a patient’s own hematopoietic stem cells, resulting in the production of functional adrenoleukodystrophy protein. As a condition of its accelerated approval, a 15-year follow-up trial (LTF-304; ClinicalTrials.gov Identifier: NCT02698579) was initiated to evaluate the long-term safety and efficacy of Skysona.

At the time of Skysona’s approval, hematologic malignancy was identified as a serious risk, with myelodysplastic syndrome (MDS) being reported in 4% of patients across all clinical studies. This safety concern prompted a Boxed Warning alongside additional risk information under the Warnings and Precautions and Clinical Trials Experience sections. 

In November 2024, the FDA issued a safety communication notifying of additional reports of hematologic malignancies, including life-threatening cases of MDS and acute myeloid leukemia. Time to diagnosis of hematologic malignancy ranged from 14 months to 10 years after initial administration of Skysona.

 As of July 2025, hematologic malignancies were diagnosed in 15% (10/67) of clinical trial patients; 9 of these patients were treated with allo-hematopoietic stem cell transplantation with or without chemotherapy. One patient developed MDS recurrence after initial treatment and 1 death related to treatment for malignancy was reported. Notably, some patients developed malignancy before a therapeutic benefit could even be attained with Skysona. 

Based on these findings, the prescribing information for Skysona has been updated to include additional safety information regarding the increased risk of hematologic malignancy, including a revision to the indication stating that Skysona should only be given to CALD patients without an available human leukocyte antigen (HLA)-matched donor for allogeneic hematopoietic stem cell transplant. 

Suspected adverse events including hematologic malignancies should be reported to the FDA’s MedWatch program and to the manufacturer, bluebird bio.

This article originally appeared on MPR