FDA Safety Investigation of Bluebird Bio's Skysona Gene Therapy Focused on Blood Cancer Risks

FDA Safety Investigation of Bluebird Bio’s Skysona Gene Therapy Focused on Blood Cancer Risks

FDA Safety Investigation of Bluebird Bio's Skysona Gene Therapy Focused on Blood Cancer Risks

Recently, the FDA revealed that it is investigating the safety profile of bluebird bio’s gene therapy known as Skysona (elivaldogene autotemcel), following new findings regarding secondary blood cancers in patients who have undergone treatment.

These safety concerns emerged after a study published in October 2024 in The New England Journal of Medicine, which identified blood cancers in seven boys who had been treated with Skysona. The researchers noted a connection between these hematologic malignancies, clonal vector insertions in cancer-associated genes, and the accumulation of mutations in genes such as CDKN2A, WT1, and KRAS.

This investigation is prompted by additional cases of hematologic malignancies reported to the FDA, including acute myeloid leukemia and myelodysplastic syndrome, with some instances classified as “life-threatening.” The cancers were diagnosed between 14 to 92 months post-treatment within clinical trials of Skysona.

The FDA advised that, considering the potential risk of hematologic malignancies, healthcare providers should thoroughly evaluate alternative treatments, like allogeneic hematopoietic stem cell transplant, for suitable patients before opting for Skysona therapy. The agency is continuing to assess if further regulatory measures are necessary.

Skysona was approved in September 2022 through the FDA’s expedited platform and is intended for use in asymptomatic or mildly symptomatic boys aged 4 to 17 diagnosed with early active cerebral adrenoleukodystrophy (CALD), a rare neurodegenerative condition primarily affecting young males, manifesting symptoms like seizures, hearing loss, and motor dysfunction.

CALD stems from mutations in the ABCD1 gene, resulting in harmful accumulation of very long-chain fatty acids within the brain and spinal cord. Skysona administers additional functional copies of the ABCD1 gene into the patients’ stem cells, which aids in decelerating the deterioration of neurologic functions.

Skysona includes a boxed warning regarding hematologic malignancies, indicating that some cases have been reported among those treated with this gene therapy.

The current inquiry into Skysona underscores the ongoing safety hurdles associated with gene therapy development. In the previous month, Neurogene faced a serious adverse event related to its investigational Rett syndrome treatment NGN-401, identified as systemic hyperinflammatory syndrome—a recognized immune-related side effect linked to high doses of adeno-associated virus vectors. Tragically, this incident culminated in the death of the patient, prompting Neurogene to withdraw the high-dose segment of its Rett syndrome trial.

Moreover, only weeks prior, Beam Therapeutics also reported a patient fatality during the Phase I/II BEACON trial associated with its base editing candidate BEAM-101 for sickle cell disease. Though the death—due to respiratory failure four months after administration—was ultimately deemed unrelated to BEAM-101, it nonetheless overshadowed otherwise promising trial results.