The FDA has significantly restricted access to bluebird bio's gene therapy Skysona following a concerning increase in blood cancer cases among treated patients. The therapy can now only be used in patients with cerebral adrenoleukodystrophy (CALD) who have no other available treatment options or suitable stem cell donors.
Cancer Risk Triples Since Approval
The regulatory action stems from post-marketing surveillance data showing a dramatic increase in hematologic malignancies. Since Skysona's accelerated approval in September 2022, the incidence of blood cancers has risen from 4% to 15% among clinical trial participants. Ten of 67 patients treated in clinical trials have now developed hematologic malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
According to the FDA's Friday release, the agency received seven additional reports of hematological malignancies since the therapy's initial approval, more than tripling the previously reported incidence rate. The blood cancers are described as "life-threatening" and can emerge anywhere from 14 months to 10 years after Skysona treatment.
Fatal Outcomes and Treatment Failures
The safety concerns have resulted in serious clinical consequences. One patient has died due to treatment for hematologic malignancy, while another experienced recurrent MDS requiring re-treatment. Particularly troubling for the FDA is that some patients developed malignancies before Skysona had sufficient time to provide therapeutic benefit for their underlying CALD condition.
"Importantly, some patients developed malignancy before Skysona had time to potentially provide therapeutic benefit for their CALD," the FDA stated in its Friday announcement.
Revised Treatment Guidelines
The regulatory changes require comprehensive updates to Skysona's prescribing information, including modifications to the boxed warning, indications and usage, warnings and precautions, and adverse reactions sections. The revised indication now restricts treatment to patients without an available human leukocyte antigen (HLA)-matched allogeneic hematopoietic stem cell donor.
Skysona is an autologous hematopoietic stem cell-based gene therapy indicated for boys aged four to 17 years with active CALD. The therapy works by delivering functional copies of the ABCD1 gene into patients' stem cells to address the underlying genetic mutation that causes brain damage and cognitive decline in CALD patients.
Impact on Bluebird Bio
The regulatory restriction comes at a challenging time for bluebird bio, which recently went private in February through an acquisition by Carlyle and SK Capital Partners. Under the deal terms, stockholders receive $3.00 per share in cash plus a contingent value right of $6.84 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.
The company did not report revenue for Skysona in the first quarter, and the new restrictions are likely to further limit the therapy's commercial potential given the significantly narrowed patient population eligible for treatment.
