FDA Restricts Patient Pool for Bluebird’s Skysona Amid Safety Concerns

The FDA has limited access to bluebird bio’s gene therapy Skysona, which can now only be used in patients with cerebral adrenoleukodystrophy for whom no other therapies or stem cell donors are available.

According to the regulator’s release on Friday, these labelling changes are linked to the heightened risk of blood cancer associated with Skysona. The FDA first flagged cases of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients infused with the gene therapy back in November 2024.

Under its original label, Skysona, which was granted accelerated approval for cerebral adrenoleukodystrophy (CALD) in 2022, already carried a boxed warning for hematologic malignancies, though it was available to all CALD patients. Across its clinical development, 3 of 67 treated patients developed MDS, resulting in an incidence rate of 4%, as per the FDA’s release on Friday.

Since approval, the FDA has received seven additional reports of hematological malignancies, meaning 10 patients of the 67 have developed blood cancers after infusion, and the incidence rate has now risen to 15%. According to the regulator’s post-marketing data, the blood cancers are “life-threatening” and can arise from 14 months to 10 years after Skysona treatment. One patient has already died due to treatment for the hematologic malignancy, while another experienced recurrent MDS that has required re-treatment.

“Importantly, some patients developed malignancy before Skysona had time to potentially provide therapeutic benefit for their CALD,” the FDA wrote on Friday.

Skysona is an autologous hematopoietic stem cell-based gene therapy indicated for boys aged four to 17 years with active CALD. CALD is caused by mutations in the ABCD1 gene, leading to brain damage and cognitive decline. Skysona delivers functional copies of the ABCD1 gene into patients’ stem cells. Bluebird, which went private in February in an acquisition deal with Carlyle and SK Capital Partners, did not report revenue for Skysona in the first quarter.

Skysona’s narrowed prescribing population comes amid broader challenges and setbacks to the gene therapy space. Most notable of these are the patient deaths associated with Sarepta’s Duchenne muscular dystrophy therapy Elevidys, which in recent weeks have caused a regulatory storm for the biotech. Meanwhile, last month, Ultragenyx’s Sanfilippo gene therapy was hit with a Complete Response Letter from the FDA, citing manufacturing issues. Earlier this year, Vertex turned its back on the adeno-associated virus vector technology.