FDA Updates Labeling for Bluebird Bio’s Gene Therapy for CALD

The FDA has updated the label for bluebird bio’s gene therapy, Skysona, restricting its use to a smaller patient population due to an increased risk of blood cancers. While Skysona was initially approved in 2022 to treat cerebral adrenoleukodystrophy (CALD), it is now only indicated for patients who do not have a suitable donor for a stem cell transplant. This change follows an FDA investigation, which was triggered by a significant rise in the reported incidence of hematologic malignancies.

Increased Risk of Blood Cancers

According to the FDA, as of July 2025, 10 out of 67 clinical trial participants (15%) have been diagnosed with blood cancers, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia. This is a considerable increase from the 4% rate reported at the time of the therapy’s initial approval. One death has been linked to the treatment for this malignancy. The risk is believed to stem from the lentiviral vector used in Skysona, which may activate cancer-causing genes when it integrates into the patient’s DNA.

Given the potential for cancer to emerge anywhere from 14 months to 10 years after treatment, the updated label requires patients to be monitored for life. This includes quarterly blood count checks and annual assessments for evidence of clonal expansion after the first year.

How Skysona Works

Skysona uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSCs). This means the genetic modification occurs outside the patient’s body. The modified cells are then reinfused, allowing them to produce the protein that is missing in CALD patients. However, the lentivirus can sometimes insert itself into a part of the patient’s DNA that controls cell growth, potentially leading to the development of blood cancers.

Commercial Impact on bluebird bio

The restriction is expected to negatively impact sales of the $3 million therapy, which already recorded no sales in the first three months of 2025. This compounds the financial difficulties for bluebird bio, which recently sold itself to Carlyle and SK Capital Partners for $49 million after struggling with commercializing its expensive, one-time gene therapies.

In contrast, bluebird’s other gene therapies—Zynteglo for beta-thalassemia and Lyfgenia for sickle cell disease—have shown more promising sales figures, with no similar cases of viral vector-related cancer reported. Lyfgenia, however, faces competition from Vertex’s rival treatment, Casgevy.