NEW YORK – The US Food and Drug Administration said it is investigating the "serious risk" of patients developing blood cancer after receiving Bluebird Bio's gene therapy for cerebral adrenoleukodystrophy (CALD), known as Skysona (elivaldogene autotemcel), and evaluating whether there's a need for further regulatory action.
The FDA last week said that since Skysona's accelerated approval in 2022, it has received additional reports of patients being diagnosed with hematologic malignancies in clinical trials of the gene therapy, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia that appear to be treatment related. These cases were diagnosed 14 to 92 months after patients received Skysona.
"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 human leukocyte antigen (HLA)-matched donor, prior to deciding to treat a child with Skysona," the FDA said in a safety update.
The additional reports of hematologic malignancies were detailed in a paper published in the New England Journal of Medicine this fall. Investigators reported at the time that seven patients, or about 10 percent, treated with Skysona in clinical trials later developed blood cancers. Most of these cancers were treatable.
It remains unclear why some patients developed cancer, but researchers said they believed the malignancies are related to the particular lentiviral vector used to deliver the gene therapy.
Bluebird, which is headquartered in Somerville, Massachusetts, in a statement stressed that the safety update from the FDA was not prompted by new cases of malignancies or other safety issues.
"Hematologic malignancy is a known risk of Skysona, and we have been engaged with the FDA on this risk since it was first identified," a company spokesperson said in an emailed statement. "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."
Skysona is designed to slow progression of CALD, a rare metabolic disorder caused by mutations in the ABCD1 gene. The gene therapy uses a Lenti-D lentiviral vector that encodes ABCD1 complementary DNA to transduce autologous CD34-positive hematopoietic stem cells, which are modified ex vivo and administered back into the body.
The FDA granted accelerated approval to Skysona as a treatment for certain boys with early-stage cerebral adrenoleukodystrophy in 2022. The agency's decision was based on Skysona's ability to improve patients' two-year survival without major functional disabilities in clinical trials.
The FDA required Bluebird to include a boxed warning about the risk of hematologic malignancies on the gene therapy's label. According to the label, physicians are encouraged to "carefully consider alternative therapies prior to the decision to treat a child" and closely monitor patients who receive the product for their entire lives.
When the FDA approved Skysona, it also included a post-marketing requirement for Bluebird to conduct a 15-year follow-up prospective, observational study to assess long-term safety and risk of secondary malignancies after treatment with the gene therapy.
Skysona carries a list price of $3 million.