FDA restricts use of bluebird’s Skysona, citing increased hematologic malignancy risk

After completing a review of clinical trial data, the FDA has determined that bluebird’s gene therapy, Skysona, should only be used in cerebral adrenoleukodystrophy (CALD) patients without suitable alternative treatment options, given the increased risk of hematologic malignancy.

Skysona (eli-cel) is an autologous hematopoietic stem cell (HSC)-based gene therapy approved in September 2022 to slow the progression of neurologic dysfunction in boys 4-17 years of age with CALD. Blood and bone marrow cancer is a known risk carried by Skysona, and was included as a boxed warning when the treatment was initially approved.

In December 2024, the agency launched a probe into the therapy after receiving additional reports of hematologic malignancies. According to the FDA, since initial approval, the agency 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.

As such, the agency 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 allogeneic hematopoietic stem cell (allo-HSC) donor.

The news is less than ideal for bluebird, which recently sold itself to global investment firms Carlyle and SK Capital Partners. Per the deal, bluebird stockholders will receive $3.00 per share in cash and a contingent value right of $6.84 per share — bringing the potential total value up to $9.84 per share — if any of bluebird’s three approved gene therapies achieves $600 million in net sales over any 12-month period by December 31, 2027.