November 27, 2024

Summary of the Issue

Since approval, the Food and Drug Administration (FDA) has received additional reports of hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia, following treatment of early, active cerebral adrenoleukodystrophy (CALD) patients with Skysona (elivaldogene autotemcel), an autologous hematopoietic stem cell (HSC)-based gene therapy. The reported cases appear to be related to treatment with Skysona. Reports were received from clinical trials, with cases diagnosed between 14 to 92 months post-treatment.

FDA is investigating the known risk of hematologic malignancies with serious outcomes, including those such as hospitalization, the requirement for allogeneic hematopoietic stem cell transplantation, and death, and is evaluating the need for further regulatory action. 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 U.S. prescribing information (USPI) includes information on the serious risk of developing hematologic malignancies following treatment with Skysona in a Boxed Warning, and under Warnings and Precautions and Clinical Trials Experience. Patients and clinical trial participants receiving treatment with Skysona should be monitored lifelong for hematologic malignancy. Early diagnosis of hematologic malignancy can be critically important. Therefore, patients should be closely monitored with complete blood counts at least every 3 months and through assessments for evidence of clonal expansion or predominance at least twice in the first year after Skysona administration and annually thereafter, and bone marrow evaluations should be considered as clinically indicated.  If hematologic malignancy is detected in a patient who received Skysona, the event should be reported to the manufacturer and instructions will be provided on collection of samples for further testing.

The approval for Skysona included a postmarketing requirement (PMR) under section 505(o) of the Federal Food, Drug, and Cosmetic Act (FDCA) to conduct a 15-year long-term follow-up prospective, observational safety study to assess the long-term safety and the risk of secondary malignancies occurring after treatment with Skysona. The study includes monitoring (at pre-specified intervals) for clonal expansion.

To report suspected adverse events including hematologic malignancies, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Healthcare providers, clinical investigators, patients, and caregivers who have questions may contact FDA’s Center for Biologics Evaluation and Research (CBER) at ocod@fda.hhs.gov.