FDA Investigates Reports of Blood Cancer Cases Linked to Gene Therapy

The U.S. Food and Drug Administration (FDA) has launched an investigation into reports of blood cancer cases linked to Skysona, a $3 million autologous hematopoietic stem cell (HSC)-based gene therapy developed by Bluebird Bio to treat the rare neurodegenerative disorder cerebral adrenoleukodystrophy (CALD). The FDA is evaluating the need for further regulatory action and has advised healthcare providers to consider alternative therapies, including allogeneic hematopoietic stem cell transplantation, before deciding whether to treat their child with Skysona.

Skysona, the First-Ever Therapy for CALD, Faces Challenges as 7 of 67 Patients Develop Malignancies in Clinical Trials

Skysona (elivaldogene autotemcel), approved on September 16, 2022, was the first ever FDA approved therapy in boys aged 4 to 17 shown to slow the progression of CALD. However, in a recent New England Journal of Medicine (NEJM) study it was found that seven out of 67 children in clinical trials developed blood cancers, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), after being treated with Skysona. The diagnoses surfaced as early as 14 months and as late as nearly eight years after treatment, highlighting the extended timeline of potential risks.

Despite the concerning reports of malignancies, the NEJM emphasized the therapy’s impact, revealing that six years after treatment, 94% of patients showed no neurological decline, and more than 80% remained free of disability. Bluebird bio acknowledged the risk of blood cancers in the prescribing information when the drug was approved, and a boxed warning was linked with its use. The FDA had also mandated a 15-year post-marketing study to monitor long-term safety and assess cancer risk.

Bluebird Bio Highlights Need for Further Study of Lentiviral Vector in Skysona to Mitigate Patient Risks

Bluebird promptly notified investigators, an independent data monitoring committee, and the FDA upon receiving reports of the cases. Notably, three of the seven hematological malignancies had already been identified when the FDA developed a regulatory action document for the therapy back in 2022.

The company linked the malignancies developed to the linkage of lentiviral vector into a proto-oncogene during Skysona’s manufacturing, noting that its other gene therapies, Zynteglo (for beta thalassemia) and Lyfgenia (for sickle cell disease), utilize self-inactivating (SIN) gamma-retroviral vectors, which differ from the vector used in Skysona. Bluebird noted that while the lentiviral vector has shown efficacy in other gene therapies, it is crucial to continue evaluating its long-term safety to mitigate risks for patients.The company emphasized that no new safety incidents have occurred as of now and reaffirmed the company’s dedication to patient safety.

Author

Denisse Sandoval