FDA investigating hematologic cancer risk in kids treated with Skysona for brain disease

The FDA announced it is investigating serious health risks associated with administration of an autologous hematopoietic stem cell gene therapy for children with early active cerebral adrenoleukodystrophy, or CALD.

In a press release, the FDA said its review was initiated based upon reports of life-threatening cases of blood-based malignancies such as myelodysplastic syndrome and acute myeloid leukemia, which required hospitalization or even resulted in death, following treatment with Skysona (elivaldogene autotemcel, Bluebird Bio), also called eli-cel.

“This update from the agency was not prompted by any new cases of malignancy or other safety updates,” a Bluebird Bio representative told Healio in an emailed statement. “Hematologic malignancy is a known risk of Skysona, and we have been engaged with the FDA on this risk since it was first identified.”

“The well-being of patients with CALD treated with Skysona, or who are considering gene therapy following a diagnosis of CALD, is our top priority and we will continue to follow our established processes to investigate and report potential safety issues,” the statement concluded.

Bluebird Bio additionally told Healio that Skysona includes a boxed warning for hematologic malignancy, and all patients should be counseled on the risk and engage in lifelong monitoring for blood-related conditions associated with treatment.

In August 2021, the FDA placed a clinical hold on a phase 3 study investigating Skysona due to an evident cancer risk. However, in June 2022 an FDA advisory committee unanimously endorsed the gene therapy, saying its benefits outweighed the risks for patients aged younger than 18 years who lacked “available and willing human leukocyte antigen-matched sibling hematopoietic stem cell donors.”

The FDA subsequently granted accelerated approval for Skysona to treat early active CALD in September 2022.

In October, analyses of data published in The New England Journal of Medicine found that while 81% of boys with CALD who received Skysona survived without functional disability over a median follow-up period of 6 years, seven patients in the treatment cohort developed hematologic cancer.

According to the FDA release, Skysona’s approval included a post-marketing requirement under the Federal Food, Drug, and Cosmetic Act for the initiation of a 15-year prospective, observational study to examine the drug’s safety, risk for secondary malignancies occurring after treatment and monitoring for clonal expansion.

While the FDA continues to monitor the situation and evaluates the need for additional regulatory action, the agency said in its release that providers should consider alternative therapies, including allogeneic hematopoietic stem cell transplant, before treatment with Skysona.