FDA further probes hematologic malignancy risk in Skysona treatment

The U.S. FDA is investigating the known risk of hematologic malignancies with serious outcomes following treatment of early, active cerebral adrenoleukodystrophy (CALD) patients with bluebird's Skysona and is evaluating the need for further regulatory action, according to a release shared by the agency last week.

Skysona (eli-cel) is an autologous hematopoietic stem cell (HSC)-based gene therapy approved in September 2022 to slow the progression of neurologic dysfunction in boys 4-17 years of age with CALD. Blood and bone marrow cancer is a known risk carried by Skysona, and was included as a boxed warning when the treatment was initially approved.

Since the therapy's approval, the FDA has received additional reports of hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia. Reports were received from clinical trials, with cases diagnosed between 14 to 92 months post-treatment.

In its recent release, the agency suggests that 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. Allogeneic hematopoietic stem cell transplants carry their own risks, including the risk of serious potential complications including death, that can increase dramatically in patients without a HLA matched donor.

CALD is a rare, progressive, neurodegenerative disease that primarily affects young boys and causes irreversible, devastating neurologic decline, including major functional disabilities such as loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement. Nearly half of patients who do not receive treatment die within five years of symptom onset.