Skysona Blood Cancer Risks Result in FDA Investigation Into Gene Therapy Treatment

Federal health officials have launched an investigation into the potential side effects of Skysona gene therapy, after identifying that recent data from clinical trials suggests that several patients developed blood cancers or leukemia in the months following treatment.

Skysona is a gene therapy drug manufactured by Bluebird Bio that is designed to treat active cerebral adrenoleukodystrophy (CALD), which is a rare genetic disorder that affects the brain and central nervous system, causing a buildup of very long-chain fatty acids that can lead to progressive neurological damage.

Common symptoms of CALD include seizures, coordination difficulties and swallowing problems, with the disease often becoming fatal within eight years of symptom onset.

Skysona gene therapy was first approved for pediatric use by the U.S. Food and Drug Administration (FDA) in September 2021, to modify a patient’s blood stem cells to address the genetic defect responsible for CALD.

The therapy is intended for children with early, active CALD who do not have a matched sibling donor available for a stem cell transplant. The therapy involves extracting these cells, treating them in a laboratory to correct the genetic anomaly, and reintroducing them into the patient’s body to reduce or halt the progression of the disease by restoring more normal cell function.

However, the U.S. Food and Drug Administration (FDA) now indicates that it is examining potential Skysoma blood cancer risks, to determine whether any regulatory actions need to be taken to protect patients.

The FDA announced that it was launching a Skysona gene therapy investigation on November 27, which will assess the risk of hematologic malignancies, including leukemia, which have led to serious outcomes such as hospitalization, the need for allogeneic hematopoietic stem cell transplantation, and death.

The investigation was opened after clinical trials identified patients treated with Skysona who developed life-threatening blood cancers, including myelodysplastic syndrome and acute myeloid leukemia, between 14 to 92 months after treatment.

The FDA is reviewing whether there may be serious side effects with Skysona, including risks that may lead to hospitalization and death, as well as the potential need for stem cell transplants following hospitalization, due to the drug’s modification of a patient’s stem cells.

As the investigation progresses, the agency is advising doctors to carefully evaluate alternative treatments, including allogeneic hematopoietic stem cell transplants for patients with compatible antigen-matched donors, before opting to treat children with Skysona.

Currently, Skysona includes a Black Box Warning, which is the strongest warning the FDA can require on a drug label, which alerts patients to significant safety risks, including the potential increased risk of certain blood cancers.

However, the FDA is advising that patients treated with Skysona be monitored for blood cancers throughout their lives, as early diagnosis is crucial. Officials indicated patients should be tested for regular blood counts every three months and monitored for clonal expansion or predominance at least twice in the first year and annually thereafter. Additionally, bone marrow evaluations should be conducted as deemed necessary.

As part of the drug’s 2022 FDA approval, a 15-year follow-up period was mandated to include evaluations and observational safety studies to monitor for any cancers that may develop post-treatment. These ongoing investigations and studies could potentially lead to modifications in the drug’s approval status in the future.

The FDA is encouraging healthcare providers and patients to report suspected adverse events including hematologic malignancies to the agency through its MedWatch Adverse Event Reporting Program by calling 1-800-FDA-1088 or reporting a problem online at www.fda.gov/medwatch.