Skysona (gene therapy)

2024: Gene therapy for nervous system diseases led to seven cases of blood cancer

In mid-October 2024, it became known that seven cases of blood cancer were detected during studies of the gene therapy Skysona manufactured by Bluebird bio.

Hemoblastoses developed in 7 of 67 patients under the age of 18 who participated in the phase II and III Skysona trials. All patients received a single dose of a hematopoietic stem cell-based drug to treat early cerebral adrenoleukodystrophy (CALD) - a rare and deadly neurodegenerative disease. In six cases, myelodysplastic syndrome (MDS) was detected, in one case - acute myeloid leukemia (AML). One MDS patient has died, four patients are in remission for both cancer and underlying disease, and another patient is awaiting treatment. The patient who developed AML successfully underwent stem cell transplantation.

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Shutterstock/ sumroeng chinnapan

Cancer developed at different times, and from the moment of administration of the drug passed from 14 months to 7.5 years. The observed cases were associated with the integration of the lentiviral vector of Skysona into the proto-oncogene, which led to uncontrolled division of blood cells. Various lentiviral vectors are also used in other gene therapy preparations manufactured by Bluebird bio. For example, the drug for the treatment of sickle cell disease Lyfgenia uses the LentiGlobin BB305 vector.

The development of secondary malignancies is a known risk of gene therapy using similar vectors, and such mutagenesis, leading to activation of proto-oncogenes or disruption of tumor suppressor genes, remains a serious problem along with the risks of acute inflammation and genotoxic side effects. The latest data do not indicate new risks, but allow the most complete and up-to-date assessment of the safety indicators of treatment.^[1]

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