FDA Restricts CALD Gene Therapy After Safety Review

The Food and Drug Administration is requiring Bluebird Bio to update the labeling for its elivaldogene autotemcel (eli-cel) gene therapy following an investigation into cases of hematologic malignancies in patients with early, active cerebral adrenoleukodystrophy (CALD) who received the treatment. The agency is also limiting the therapy, marketed as Skysona, to patients without a suitable human leukocyte antigen (HLA)-matched allogeneic hematopoietic stem cell donor.

Since its approval in 2022, 10 of 67 participants treated with eli-cel during clinical trials have developed hematologic malignancies, including life-threatening cases of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Nine of the 10 affected patients underwent allogeneic hematopoietic stem cell transplantation, with or without chemotherapy, and one treatment-related death has occurred. Additionally, FDA emphasized that some patients developed malignancies before eli-cel had time to provide potential therapeutic benefit for their CALD.

The updates include changes to the boxed warning, indications and usage, warnings and precautions, and adverse reactions – clinical trials experience sections of the prescribing information. An updated medication guide includes new safety information on the increased risk of hematologic malignancy. Finally, FDA emphasized that, given the increased risk of hematological malignancy, eli-cel should only be used in CALD patients without suitable alternative treatment options.