FDA Restricts Gene Therapy Skysona Due to Blood Cancer Risk

 The FDA approved labeling changes for elivaldogene autotemcel (eli-cel; Skysona bluebird bio), a one-time gene therapy for patients with early, active cerebral adrenoleukodystrophy (CALD), to reflect new safety information about hematologic malignancy risk, the agency announced

opens in a new tab or window Friday.

The update restricts the eli-cel indicationopens in a new tab or window to patients without an available human leukocyte antigen (HLA)-matched allogeneic hematopoietic stem cell donor. Given the risk of blood cancer, eli-cel should be used only in CALD patients without suitable alternative treatment options, the agency said.

The notice follows an FDA investigation of reportsopens in a new tab or window of blood cancers -- including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia -- in patients with early, active CALD who were treated with eli-cel.

In 2022, the FDA granted accelerated approval to eli-celopens in a new tab or window to treat CALD in boys ages 4 to 17 years. Childhood CALD is a rare debilitating form of adrenoleukodystrophy that generally occurs in young boys. It's caused by a mutation in the ABCD1 gene that leads to the overproduction of very long-chain fatty acids primarily in the white matter of the brain and spinal cord that destroys myelin.

When eli-cel was approved, hematologic malignancy was identified as a serious risk and myelodysplastic syndrome was reported in three of 67 patients (4%) across clinical studies. Since then, the FDA received seven more blood cancer reports from clinical trial participants. As of July, hematologic malignancies have been diagnosed in 10 of 67 (15%) participants.

Reports suggest that blood cancer diagnoses occurred from 14 months to 10 years after eli-cell administration, the FDA said. Nine of the 10 patients with blood cancer were treated with allogeneic hematopoietic stem cell transplantation, with or without chemotherapy.

"The malignancies are life-threatening conditions, and one death related to treatment for malignancy has occurred," the agency reported. "One patient developed recurrence of myelodysplastic syndrome after initial treatment, which required re-treatment." Some patients developed cancer before eli-cel had time to provide therapeutic benefit for CALD.

Patients and clinical trial participants receiving eli-cel treatment should be monitored for life for hematologic malignancy, the FDA stated. Patients should complete blood count checks at least every 3 months and have thorough assessments for evidence of clonal expansion or predominance at least twice in the first year after eli-cel administration and annually thereafter. Bone marrow evaluations should be considered as clinically indicated.

Eli-cel's approval included a postmarketing requirement for a 15-year follow-up prospective study to assess long-term safety and the risk of secondary malignancies occurring after treatment. The study includes monitoring for clonal expansion.

https://www.medpagetoday.com/neurology/generalneurology/116922