After telegraphing an investigation in November, the FDA has moved to restrict the use of bluebird bio’s gene therapy Skysona in certain patients.
The FDA has updated Skysona’s indication, allowing it to be used only in patients who do not have an available human leukocyte antigen (HLA)-matched donor for stem cell transplant. The one-time therapy is approved to treat cerebral adrenoleukodystrophy (CALD), a rare inherited neurological disorder in which the accumulation of harmful fatty acids in the bloodstream damages the protective myelin sheath around nerve fibers.
The FDA decided that Skysona should not be used in patients with alternative treatment options due to concerns of an increased risk of blood cancer.
Hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia, are a known risk factor for Skysona since its approval in 2022 and are reflected in a boxed warning on the drug’s label. The malignant transformation is believed to be likely caused by an insertion of Skysona’s lentiviral vector into the human genome.
But an increase in cancer cases triggered an FDA investigation in November 2024, with a regulatory request to update the label this April, according to bluebird.
As of July 2025, hematologic malignancies have been diagnosed in 10 (15%) of 67 clinical trial participants, compared with three (4%) incidents at the time of Skysona’s initial approval, according to the FDA. There’s one death related to treatment for the cancer.
Existing reports showed no obvious pattern as to when cancer might emerge, as diagnoses ranged from 14 months to 10 years after Skysona administration. However, as the FDA highlighted, some patients developed cancer even before experiencing any therapeutic benefit from the gene therapy.
As such, patients are advised to be monitored for blood cancer their entire life. Skysona’s boxed warning asks that patients go through complete blood count checks at least every three months and thorough assessments for evidence of clonal expansion or predominance annually after the first year of treatment.
Skysona, with a list price of $3 million per treatment, recorded no sales in the first three months of 2025. Beta-thalassemia therapy Zynteglo saw its sales rise to $26.3 million during the first quarter, compared with $18.6 million a year ago. The sickle cell disease gene therapy Lyfgenia brought in $12.4 million in sales during the period, while Vertex’s rival CRISPR-based treatment Casgevy pulled in $14.2 million.
No cases of cancer caused by viral vector insertion have been identified in patients treated with Zynteglo or Lyfgenia, bluebird said in its quarterly report filed in May.
As commercial progress of the three gene therapies fails to impress and a debt payment nears its due date, bluebird bio recently sold itself to Carlyle and SK Capital Partners for $49 million, or $5 per share, following some investor resistance to a previous lower offer price.
The acquisition also offers an alternative payment method, which includes a $3-per-share payment upfront and $6.84-apiece contingence value rights, which are payable if bluebird’s three marketed products reach $600 million over a 12-month period by the end of 2027.