FDA Restricts Bluebird Bio's Gene Therapy Skysona Amid Blood Cancer Concerns

The U.S. Food and Drug Administration (FDA) has imposed restrictions on bluebird bio's gene therapy Skysona following reports of increased blood cancer incidence among treated patients. This development marks a significant setback for the company and raises questions about the long-term safety of certain gene therapies.

Skysona's Indication Update and Safety Concerns

The FDA has updated Skysona's indication, now limiting its use to patients with cerebral adrenoleukodystrophy (CALD) who do not have an available human leukocyte antigen (HLA)-matched donor for stem cell transplant. This restriction comes in response to an alarming increase in hematologic malignancies observed in clinical trial participants.

As of July 2025, 10 out of 67 (15%) clinical trial participants have been diagnosed with blood cancers, including myelodysplastic syndrome and acute myeloid leukemia. This represents a significant increase from the 4% incidence rate reported at the time of Skysona's initial approval in 2022. One death related to cancer treatment has been reported.

The FDA's decision underscores the potential risks associated with lentiviral vector-based gene therapies. The malignant transformation is believed to be caused by the insertion of Skysona's lentiviral vector into the human genome, a known risk factor that was previously included in the therapy's boxed warning.

Enhanced Monitoring and Patient Safety Measures

In light of these developments, the FDA has mandated enhanced monitoring protocols for patients treated with Skysona. Patients are now advised to undergo lifelong monitoring for blood cancer, with complete blood count checks recommended at least every three months. Additionally, thorough annual assessments for evidence of clonal expansion or predominance are required after the first year of treatment.

The FDA highlighted that some patients developed cancer even before experiencing therapeutic benefits from Skysona, emphasizing the unpredictable nature of this serious side effect. The time frame for cancer emergence varied widely, with diagnoses ranging from 14 months to 10 years post-treatment.

Impact on Bluebird Bio and Industry Implications

The restrictions on Skysona, which carries a list price of $3 million per treatment, come at a challenging time for bluebird bio. The company reported no sales for Skysona in the first quarter of 2025, while its other gene therapies, Zynteglo and Lyfgenia, showed modest sales growth.

In response to commercial challenges and approaching debt obligations, bluebird bio recently agreed to be acquired by Carlyle and SK Capital Partners for $49 million, or $5 per share. The deal includes an alternative payment structure with contingent value rights tied to future product performance.

These developments raise broader questions about the safety and commercial viability of gene therapies, potentially impacting investor confidence and regulatory scrutiny across the industry. As the field continues to evolve, balancing innovation with patient safety remains a critical challenge for both companies and regulators.