The cancers were diagnosed 19 to 92 months after Skysona treatment.
The FDA last week announced that it is looking into the safety of bluebird bio’s gene therapy Skysona (elivaldogene autotemcel) after new reports of secondary blood cancers in treated patients.
The new safety signals follow an October 2024 study published in The New England Journal of Medicine, which detected blood cancers in seven boys who had received Skysona. Researchers linked the hematologic malignancies to clonal vector insertions in cancer genes as well as to the build-up of mutations in several genes of interest, including CDKN2A, WT1 and KRAS.
The investigation comes after the regulator documented additional cases of hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndrome—some cases of which were deemed “life-threatening” by the FDA. These reports came from clinical trials of Skysona, with the cancers diagnosed from 14 to 92 months after treatment.
“Given the risk of hematologic malignancy, providers should carefully consider alternative therapies, including allogeneic hematopoietic stem cell transplant for patients who have a suitable, willing, and available … donor, prior to deciding to treat a child with Skysona,” the FDA wrote in its announcement last week, noting that it is still “evaluating the need for further regulatory action.”
Approved in September 2022 under the FDA’s accelerated pathway, Skysona is indicated for asymptomatic or mildly symptomatic boys aged 4 to 17 years with early active cerebral adrenoleukodystrophy (CALD), a rare and progressive neurodegenerative disease that occurs mostly in young boys and is characterized by symptoms such as seizures, deafness and motor problems.
CALD is caused by mutations in the ABCD1 gene, which lead to the pathologic accumulation of very long-chain fatty acids in the brain and spinal cord. Skysona counters this by delivering additional functional copies of the ABCD1 gene into patients’ stem cells, allowing the gene therapy to slow the progression of neurologic dysfunction.
Skysona’s label carries a boxed warning for hematologic malignancies, pointing out that some cases have “occurred in patients with Skysona.”
Last week’s probe into Skysona further highlights the safety challenges of developing gene therapies. Last month, Neurogene’s investigational Rett syndrome treatment NGN-401 was linked to a serious adverse event in one patient, characterized as systemic hyperinflammatory syndrome—a known immune-related toxicity typically associated with high doses of adeno-associated virus vectors.The patient later died, leading Neurogene to discontinue the high-dose arm of its Rett syndrome study.
Just weeks earlier, Beam Therapeutics likewise reported a patient death in the Phase I/II BEACON trial for its base editing candidate BEAM-101, being developed for sickle cell disease. The death, which was caused by respiratory failure four months after dosing, was ultimately deemed unrelated to BEAM-101, but nevertheless tainted Beam’s otherwise encouraging data.
