Elivaldogene autotemcel FDA Alerts

FDA Approves Required Labeling Changes for Increased Risk of Hematologic Malignancy Following Treatment with Skysona (elivaldogene autotemcel)

August 7, 2025 -- In November 2024, FDA issued a safety communication, “FDA Investigating Serious Risk of Hematologic Malignancy Following Skysona (elivaldogene autotemcel),” to provide information on additional reports of hematologic malignancies, including life-threatening cases of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), following treatment of early, active cerebral adrenoleukodystrophy (CALD) patients with Skysona (elivaldogene autotemcel), a lentiviral autologous hematopoietic stem cell (HSC)-based gene therapy.  At the time of initial approval of Skysona in 2022, hematologic malignancy was identified as a serious risk, with MDS reported in 3 of 67 patients (4%) across clinical studies. Since initial approval, FDA has received seven additional reports from clinical trial participants, and as of July 2025, hematologic malignancies have been diagnosed in 10/67 (15%) clinical trial participants, more than tripling the previously reported incidence.

Current reports suggest that the time to diagnosis of hematologic malignancy ranges from 14 months to 10 years after Skysona administration. Nine of the 10 patients have been treated with allo-HSCT (with or without chemotherapy) for the hematologic malignancy. The malignancies are life-threatening conditions, and one death related to treatment for malignancy has occurred. One patient developed recurrence of MDS after initial treatment, which required re-treatment. Importantly, some patients developed malignancy before Skysona had time to potentially provide therapeutic benefit for their CALD.

FDA has completed a review of the clinical trial data and has required updates to the Boxed Warning, Indications and Usage, Warnings and Precautions, and Adverse Reactions – Clinical Trials Experience sections of the prescribing information and Medication Guide to include new safety information on the increased risk of hematologic malignancy. Notably, the revised Indications and Usage restricts the indication to patients without an available human leukocyte antigen (HLA)-matched allogeneic hematopoietic stem cell (allo-HSC) donor. Therefore, Skysona should only be used in CALD patients without suitable alternative treatment options, given the increased risk of hematologic malignancy. The Limitations of Use section retains language emphasizing careful consideration of appropriateness and timing of treatment.

Postmarketing studies and safety monitoring

Skysona received accelerated approval on September 16, 2022, for the treatment of boys 4-17 years of age with early, active CALD, and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Additionally, 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.

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 FDA and the manufacturer and instructions will be provided on collection of samples for further testing.

Continuous monitoring and assessment of the safety of all biologics, including Skysona, is an FDA priority and we remain committed to informing the public when we learn new information about these products.

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

Source: FDA

FDA Investigating Serious Risk of Hematologic Malignancy Following Skysona (elivaldogene autotemcel)

November 27, 2024 -- 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.

Source: FDA